Synthesis of novel bioactive pyrido[2,3-d]pyrimidine derivatives with potent cytotoxicity through apoptosis as PIM-1 kinase inhibitors.

Direct synthesis and cytotoxicity activity of new series of pyrido[2,3-d]pyrimidine was described. Nicotinamide 2 was synthesized via cyclization of N-cyclohexyl derivative with cyanoacetamide. The o-aminonicotinonitrile 2 was subjected to acylation or thio acylation process followed by intramolecular heterocyclization to afford the desired pyrido[2,3-d]pyrimidine (3-10) and pyrido triazine 11. Compounds 4 and 11 exhibited remarkable cytotoxicity against MCF-7 cells with IC50 values of 0.57 µM and 1.31 µM and IC50 values of 1.13 µM and 0.99 µM against HepG2 cells. Interestingly, compounds 4 and 10 had potent PIM-1 kinase inhibition with IC50 values of 11.4 and 17.2 nM, respectively, with inhibition of 97.8% and 94.6% compared to staurosporine (IC50 = 16.7 nM, with 95.6% inhibition). Moreover, compound 4 significantly activated apoptosis in MCF-7 cells, increasing the cell apoptosis by 58.29-fold by having 36.14% total apoptosis in treated cells compared to 0.62% for control. Moreover, it arrested the cell cycle at the G1 phase. PIM-1 kinase inhibition was virtually elucidated by the molecular docking study, highlighting binding interactions of the lead compound 4 towards the PIM-1 protein. Accordingly, compound 4 was validated as a promising PIM-1 targeted chemotherapeutic agent to treat breast cancer.

Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

Female Pattern Hair Loss and Negative Psychological Impact: Possible Role of Brain-derived Neurotrophic Factor (BDNF).

INTRODUCTION: Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in females. Women with FPHL may suffer from psychological distress and defective social functioning. Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic marker for negative psychological impact in FPHL patients. OBJECTIVES: Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the severity of alopecia and the degree of psychological impact. METHODS: Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire. Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using the ELISA technique. RESULTS: Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck depression inventory score and PSS questionnaire scores. There is a significant negative correlation between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS questionnaire scores. CONCLUSIONS: Patients with FPHL are at a high risk to develop chronic stress and depression. The serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL patients.

Assessment of the physicochemical and sensory characteristics of fermented camel milk fortified with Cordia myxa and its biological effects against oxidative stress and hyperlipidemia in rats.

Natural feed additives and their potential benefits in production of safe and highly nutritious food have gained the attention of many researchers the last decades. Cordia myxa is a nutrient-dense food with various health benefits. Despite this fact, very limited studied investigated the physicochemical and sensory impacts of incorporation of fermented camel milk with Cordia myxa and its biological effects. The current study aimed to assess the physical, chemical, and sensory characteristics of fermented camel milk (FCM) fortified with 5, 10, and 15% Cordia myxa pulp. The study demonstrated that fortification of camel milk efficiently enhanced protein, total solids, ash, fiber, phenolic substance, and antioxidant activity. When compared to other treatments, FCM supplemented with 10% Cordia myxa pulp had the best sensory features. In addition, FCM fortified with 10% Cordia myxa pulp was investigated as a potential inhibitor of hypercholesterolemia agents in obese rats. Thirty-two male Wistar rats were split into two main groups including normal pellet group (n = 8) served as negative control group (G1) and a group of hyperlipidemic animals (n = 24) were feed on a high-fat diet (HFD). Hyperlipidemic rats group (n = 24) were then divided into three subgroups (8 per each); second group or positive control (G2) which include hyperlipidemic rats received distilled water (1 mL/day), the third group (G3) involved hyperlipidemic rats feed on FCM (10 g/day) and the fourth group (G4) included hyperlipidemic animals feed on 10 g/day FCM fortified with 10% of Cordia myxa pulp by oral treatment via an intestinal tube for another 4 weeks. In contrast to the positive control group, G4 treated with Cordia myxa showed a substantial decrease in malondialdehyde, LDL, cholesterol, triglycerides, AST, ALT, creatinine, and urea levels, while a significant increase in HDL, albumin, and total protein concentrations. The number of large adipocytes decreased while the number of small adipocytes increased after consumption of fortified FCM. The results indicated that fermented milk fortified with Cordia myxa pulp improved the functions of the liver and kidney in hyperlipidemic rats. These results demonstrated the protective effects of camel milk and Cordia myxa pulp against hyperlipidemia in rats.

Comparison of latissimus dorsi tendon transfer with subscapularis release versus sliding of internal rotation contracture in obstetrical brachial plexus paralysis sequela.

BACKGROUND: The purpose of this study was to compare the functional results of latissimus dorsi (LD) tendon transfer with those of subscapularis (SS) muscle release versus sliding. METHODS: Fifty-six patients with internal rotation contracture and external rotation (ER) weakness as sequelae of Erb's palsy were included in the study. Of the patients, 24 were included in group 1 (11 boys and 13 girls), with a mean age of 2 years 8 months (range 1.5-5 years) and a follow-up period of 62 months (range 38-68 months). The patients in group 1 underwent LD tendon transfer, with internal rotation contracture and SS release procedures. Thirty-two patients were included in group 2 (18 boys and 14 girls), with a mean age of 2 years 6 months (range 1.5-4.8 years) and a follow-up period of 58 months (range 38-68 months). The patients in group 2 underwent LD tendon transfer with SS sliding. RESULTS: A significant improvement in preoperative passive ER from - 3.6° to 67.3° after operation was observed in group 1. In group 2, preoperative passive ER in adduction improved from 0° to 72.3°. We found no significant difference (P = 0.1) in postoperative improvement in active ER in both groups (group 1 vs. group 2: 75° vs. 77.3°). Similarly, no significant difference (P = 0.7) in postoperative improvement in passive ER was found between the groups (group 1 vs. group 2: 71° vs. 72.3°). CONCLUSIONS: LD tendon transfer with SS release or sliding is an effective procedure to improve shoulder ER in patients with OBPP, with no inferiority of SS muscle release or sliding for internal rotation contractures and increased passive range of shoulder motion. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Comparison; Treatment Study.

Serum miR-34a-5p and miR-199a-3p as new biomarkers of neonatal sepsis.

BACKGROUND: Neonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition. PATIENTS AND METHODS: A total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p. RESULTS: miR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis. CONCLUSION: miR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.

Diagnostic role of lncRNA GAS5 and its genetic polymorphisms rs2067079, rs6790 and rs17359906 in rheumatoid arthritis.

The aim of the present study was to detect the serum levels of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in patients with rheumatoid arthritis (RA) and healthy controls, and determine the association between the rs2067079, rs6790, and rs17359906 single-nucleotide polymorphisms (SNPs) of lncRNA GAS5 gene with RA risk in the Egyptian population. Reverse transcription-quantitative PCR and real-time PCR were used to measure the serum levels of lncRNA GAS5 and genotype the two distinct alleles at the SNP sites of lncRNA GAS5 gene in 200 patients with RA and 150 controls. The mean serum levels of lncRNA GAS5 were significantly lower in the patients with RA compared with the controls (P<0.0001), and the serum levels of lncRNA GAS5 were significantly negatively associated with erythrocyte sedimentation rate, C-reactive protein levels and anti-cyclic citrullinated peptide levels in the patients with RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA [TT vs. CC: Odds ratio (OR)=2.358; 95% confidence interval (CI), 1.114-5.131; P=0.045) and the risk of rs2067079 SNP reduced with a recessive pattern (TT vs. TC + CC: OR=2.374; 95% CI, 1.091-5.123; P=0.037). rs6790 SNP was associated with RA risk in the recessive model (AA vs. GA + GG: OR=2.55; 95% CI=1.39-5.32; P=0.02). No significant associations were noted between the rs17359906 SNP and RA risk (P>0.05) or between the lncRNA GAS5 levels and their respective genotypes at the three SNPs in patients with RA (all P>0.05). Based on the results of the present study, lncRNA GAS5 may serve as a biomarker for the early detection of RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA, and a reduced risk of rs2067079 SNP was observed with a recessive pattern. rs6790 SNP was associated with RA risk in the recessive model.

Balloon-assisted sacroplasty as a successful procedure for osteoporotic sacral insufficiency fractures after failure of the conservative treatment.

Osteoporotic vertebral fractures without prior adequate traumatization are frequent diagnosed in orthopedics because of the increasing life expectancy and incidence of osteoporosis. The associated high mortality is caused by reduced mobilization which leads to a higher risk of infection and a bedridden state. On the other hand the diagnosis of sacral insufficiency fractures is often prolonged because of unspecific symptoms while being associated with similar risks. This article presents an overview of the present scientific literature and a retrospective analysis of patients treated via balloon-assisted sacroplasty. In 8 years, ten patients (three men and seven women) were treated. The average age was 78.4 years and the average time until the diagnosis 4.6 weeks. In most patients a significant pain reduction after the failure of conservative treatment thanks to operative treatment as well as increased mobility was observed. Only one experienced a minor surgical complication being cement leakage with nerval impaction which did not compromise her clinical outcome or satisfaction with the procedure. Balloon-assisted sacroplasty can possibly be seen as an effective symptomatic therapy in osteoporotic insufficiency fractures.

Maternal Δ-aminolevulinic acid dehydratase 1-2 genotype enhances fetal lead exposure and increases the susceptibility to the development of cerebral palsy.

Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p < 0.001) elevation of BLL in CP cases and their mothers that was positively correlated (r = 0.436, p < 0.05). There were progressive decreases in δ-ALAD activity with increasing BLL in both children and mothers (p < 0.05). There were non-significant (p > 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p < 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.

Scaphoid excision with lunatocapitate fusion for the treatment of scaphoid nonunion with advanced collapsed wrist.

PURPOSE: To investigate the union rate after lunatocapitate arthrodesis for the treatment of scaphoid nonunion advanced collapse (SNAC) wrists and to evaluate the clinical results of this technique. METHODS: We conducted a prospective study between January 2014 and July 2017. Fifteen males with painful stage III SNAC wrists (average age, 32 years, range, 20-37 years; average follow-up time, 25.2 months, range, 20-36 months) underwent scaphoid excision and lunatocapitate fusion. Lunatocapitate fusions were fixed with headless Herbert screws with K-wire fixation (retrograde direction). Radiographs, wrist range of motion, and Mayo wrist score were examined. RESULTS: All patients achieved radiographic and clinical union after lunatocapitate fusion during follow-up (average 10 months post-operatively). The flexion-extension arc was 70°, and the average Mayo wrist score was 74.3 points (eight with excellent, four with good, three with satisfactory, and one with poor result). Thirteen patients returned to work, whereas two with nonunion required surgical graft revision. Complete union was achieved at an average of 12 weeks after graft revision, with improved range of motion, and the patients returned to work with a change in their occupation. CONCLUSIONS: Lunatocapitate arthrodesis is a satisfactory therapeutic alternative to four-corner fusion for SNAC wrists.

Posterior Interosseous Neurectomy Alternative for Treating Chronic Wrist Pain.

Background Wrist denervation is one of the several available options for treating chronic wrist pain; partial wrist denervation performed through a single dorsal incision by resecting the distal posterior interosseous nerve provides good outcomes. Questions/Purposes This study evaluated the results of posterior interosseous neurectomy (PIN) in patients with chronic wrist pain secondary to scaphoid nonunion advanced collapse (SNAC) and scapholunate advanced collapse (SLAC). Methods In total, 30 wrists obtained from 28 patients (25 males, 3 females) were assessed. The dominant hands of 25 (right-handed) patients, nondominant hands of 5, and both hands of 2 were considered. The average age at the time of surgery was 35 (range: 19-50) years, and the average follow-up duration was 18 (range: 12-30) months. Fifteen and 13 patients had wrists with SNAC and SLAC, respectively, and all of those underwent PIN performed through the dorsal approach. The pre- and postoperative range of motion, grip strength, and pain relief percentage were recorded for all the 30 wrists. Results The average postoperative Disabilities of the Arm, Shoulder and Hand score was 30 (range: 20-80), and the difference between the pre- and postoperative scores was statistically significant. Ninety percent of the patients were satisfied with the results of PIN and reported improvement in grip strength and pain relief. Conclusions Thus, PIN may be an effective surgical technique for wrist reconstruction. Clinical Relevance To help patients challenge pain and maintain their wrist joint range of motion.

The first survey of the Saudi Acute Myocardial Infarction Registry Program: Main results and long-term outcomes (STARS-1 Program).

BACKGROUND: Prior acute coronary syndrome (ACS) registries in Saudi Arabia might not have accurately described the true demographics and cardiac care of patients with ACS. We aimed to evaluate the clinical characteristics, management, and outcomes of a representative sample of patients with acute myocardial infarction (AMI) in Saudi Arabia. METHODS: We conducted a 1-month snap-shot, prospective, multi-center registry study in 50 hospitals from various health care sectors in Saudi Arabia. We followed patients for 1 month and 1 year after hospital discharge. Patients with AMI included those with or without ST-segment elevation (STEMI or NSTEMI, respectively). This program survey will be repeated every 5 years. RESULTS: Between May 2015 and January 2017, we enrolled 2233 patients with ACS (mean age was 56 [standard deviation = 13] years; 55.6% were Saudi citizens, 85.7% were men, and 65.9% had STEMI). Coronary artery disease risk factors were high; 52.7% had diabetes mellitus and 51.2% had hypertension. Emergency Medical Services (EMS) was utilized in only 5.2% of cases. Revascularization for patients with STEMI included thrombolytic therapy (29%), primary percutaneous coronary intervention (PCI); (42.5%), neither (29%), or a pharmaco-invasive approach (3%). Non-Saudis with STEMI were less likely to undergo primary PCI compared to Saudis (35.8% vs. 48.7%; respectively, p <0.001), and women were less likely than men to achieve a door-to-balloon time of <90 min (42% vs. 65%; respectively, p = 0.003). Around half of the patients with NSTEMI did not undergo a coronary angiogram. All-cause mortality rates were 4%, 5.8%, and 8.1%, in-hospital, at 1 month, and at 1 year, respectively. These rates were significantly higher in women than in men. CONCLUSIONS: There is an urgent need for primary prevention programs, improving the EMS infrastructure and utilization, and establishing organized ACS network programs. AMI care needs further improvement, particularly for women and non-Saudis.

Synthesis of Nucleosides and Non-nucleosides Based 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles as Antiviral Agents.

BACKGROUND: Viral diseases are considered main threats that face the humanity worldwide. The emergence of new viruses like influenza viruses emphasizes the significance of designing novel antiviral drugs. METHOD: The aim of this work is to synthesize a new set of nucleoside and non-nucleoside cyanopyridine, characterized and evaluated for their in vitro antiviral properties against various strains. CONCLUSION: More of the compounds showed variable antiviral potential against a panel of eighteen DNA and RNA viruses. The screening data suggested that the order of activity of the active compounds are in the order of O-glycosyl > O-alkyl > N-alkyl > S-alkyl derivatives. In addition, the 4-fluoro substituted compounds are more effective among the O- and N-alkyl analogs, whereas remarkable antiviral activity was ascribed to the methoxylated O-glycosyl derivatives. Most of the active compounds proved to be more selective towards the inhibition of the replication of DNA rather than the RNA-viruses. The analogs 1a, 2a, 12b, 14b and 16b possessed broad spectrum and noticeable antiviral potential against most of the tested DNA- and RNA-viruses (EC50 ≈ 0.8-20 µM), accompanied with considerably low cytotoxic margin (MCC ≈ 4-20 µM), and comparable with reference standard antiviral agents.

Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues.

Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, (1)H, (13)C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.

Workplace violence against emergency versus non-emergency nurses in Mansoura university hospitals, Egypt.

Workplace violence (WPV) against nurses is a common but neglected problem in Egypt. The objectives are to estimate the prevalence and associated risk factors of different types of violence against nurses working in the emergency hospital compared with those working in non-emergency clinics, circumstances of violence, type of perpetrators, and victims' response. This cross-sectional comparative study was carried out at Mansoura University Hospitals, Egypt, during January 2013. The data were collected through the adapted version of a self-administered questionnaire developed by the International Labor Office/International Council of Nurses/World Health Organization/Public Services International on WPV in the health sector. All types of WPV are common among nurses. Precipitating factors for violent incidents identified by respondents are emergency specialty, having work shift, and younger age. Violent incidents result in work dissatisfaction and consequently impair work productivity. Nurses working in emergency hospital experienced a higher level of different types of WPV. There is an urgent need to formulate and implement a policy for dealing with violent events.

Synthesis and antimicrobial activity of some 2-pyridone nucleosides containing a sulfonamide moiety.

Glycosylation of 2-pyridonesulfonamide 1a,b with glycosyl/galactosyl bromide gave the corresponding glycosides 2a,b, 3a,b, 6a,b, and 7a,b, respectively. Deacetylation of the resulting glycosides gave the corresponding glycosides 4a,b, 5a,b, 8a,b, and 9a,b, respectively, in good yields. Furthermore, reaction of 2-pyridonesulfonamide 1b with lactosyl bromide gave a mixture the corresponding N, O-lactosides 10 and 11, which were deacetylated to give the corresponding glycosides 12 and 13, respectively. The structures of the new synthesized compounds were characterized by using IR, 1H, 13C NMR spectra, and microanalysis. Selected members of these compounds were screened for antimicrobial activity.

Synthesis of acyclovir and HBG analogues having nicotinonitrile and its 2-methyloxy 1,2,3-triazole.

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, (1)H, (13)C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.

Synthesis, antitumor and antimicrobial activities of 4-(4-chlorophenyl)-3-cyano-2-(ß-O-glycosyloxy)-6-(thien-2-yl)-nicotinonitrile.

4-(4-Chlorophenyl)-3-cyano-6-(thien-2-yl)-1H-pyridin-2-one (2) was obtained by reaction of 2-acetyl thiophene with 4-chlorobenzaldehyde and ethyl cyanoacetate in presence of ammonium acetate or by the reaction of α,ß-unsaturated compound 1 with ethyl cyanoacetate in the presence of ammonium acetate. 4-(4-Chlorophenyl)-2-(2',3',4',6'-tetra-O-acetyl-ß-d-gluco/galactopyranosyloxy)-6-(thien-2-yl)nicotinonitrile (5a and 5b), riboside 11, xyloside 12 and lactoside 16 were prepared by the reaction of 2 with glycosyl/galactosyl/xylosyl/lactosyl bromide and peracetylated xylose/ribose under the conventional and microwave irradiation methods. The reaction has regioselectively gave the O-glycosides and not the N-glycosides. The glycosides 5a,b, riboside 11, xyloside 12 and lactoside 16 were deacetylated in the presence of Et(3)N/MeOH and few drops of water to give 7a,b, 13, 14 and 17. The structure of the new synthesized compounds was confirmed by using IR, (1)H, (13)C NMR spectra and microanalysis. Selected members of these compounds were screened for antitumor and antibacterial activity.

The effect of use of dates on serum potassium in nondiabetic hemodialysis patients.

Hyperkalemia is common in patients with ESRD and may contribute to mortality. Dates have been reported to be high in potassium content. One of the concerns on hemodialysis (HD) is convincing patients to give up ingestion of dates as a part of their diet. To determine the effect of dates on serum potassium on patients, we studied 9 (M: F, 6:3, mean age 47.6) non diabetic patients on chronic hemodialysis, without evidence of hyperkalemia on monthly labs. Nearly all the patients had been on dialysis for an average of four years. The average monthly potassium was 4.6 mmol/L. The patients ingested 100 gm of dates (Rothana and Sukari) on two separate dialysis sessions. Serum potassium was measured at two and four hours post ingestion along with ECG monitoring. The patients underwent their regular dialysis as scheduled. The patients acted as their own controls and underwent the same protocol with 20meq of KCl on a separate session. The potassium levels did not change significantly over the four hours with either variety of dates or with potassium solution. Combining the two types of dates resulted in a trend towards higher potassium levels than with KCl, but it did not reach statistical significance. We conclude that in selected HD patients without hyperkalemia, ingestion of a few dates does not cause significant hyperkalemia and could be allowed on days of dialysis prior to their dialysis sessions.