Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies.

The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.

Design, synthesis and bioactivity study on oxygen-heterocyclic-based pyran analogues as effective P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based pyran analogues (4a-l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a-l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a-c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO2, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a-c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC50 = 5.0-10.7 µM. The Rho123 accumulation assay showed that compounds 4a-c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a-c derivatives showed high oral bioavailability, but they did not cross the blood-brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.

Naproxen as a potential candidate for promoting rivastigmine anti-Alzheimer activity against aluminum chloride-prompted Alzheimer's-like disease in rats; neurogenesis and apoptosis modulation as a possible underlying mechanism.

BACKGROUND AND AIM: Alzheimer's disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. We tested the hypothesis that naproxen administration to the rivastigmine-treated aluminum chloride (AlCl3) Alzheimer's rat model could provide an additive neuroprotective effect compared to rivastigmine alone. MATERIALS AND METHODS: The studied groups were control (Cont), AlCl3 treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats' memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. Activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. RESULTS: AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity; massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. CONCLUSION: Naproxen's efficacy was established by its ability to function at the cellular level, improved neurogenesis, and decreased, apoptosis without having an additional mitigating impact on cognitive impairment in rivastigmine-treated AD rats.

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects.

ß-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F2, 2,3-Cl2, 2,5-Cl2 and 3,4-Cl2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.

Nerve conduction study findings and their predictors in clinically diagnosed patients with carpal tunnel syndrome in a Saudi population.

BACKGROUND: Despite the reports of carpal tunnel syndrome (CTS) being commonplace in Saudi Arabia, there is scarcity of cross-sectional or prospective studies detailing the profile of nerve conduction study (NCS) findings in patients with CTS. OBJECTIVE: The study aimed to evaluate the neurophysiologic profile of CTS with the view to finding the determinant of abnormal findings in clinically diagnosed cases of CTS in a population of Saudis. METHODS: Nerve conduction study was performed on consecutive patients with clinically diagnosed CTS. Median sensory, ulnar sensory, radial sensory median motor and ulnar motor nerves were assessed. The nerve conduction parameters measured were median and ulnar sensory peak latency, amplitude and velocity. Median conduction velocity, distal latency, and amplitude were also measured. Comparative median-ulnar and median-ulnar-digit 4 studies were done and the severity of CTS was determined. Data was analyzed using STATA software version 12. RESULTS: A total of 152 patients, comprising 59 males and 93 females (mean age of 42.7 years) with clinically diagnosed CTS were seen during the study period. About 72.4% patients had numbness and paresthesia in the affected fingers, 66.5% had pain in the hands, and 10.5% had weakness in the affected hands. Majority of the patients (62%) had bilateral clinical features. Carpal tunnel syndrome was confirmed with NCS in 84 (55.26%) patients. Presence of weakness in the affected hand, positive Phalen' sign, and positive Tinel's sign in patients appear to predict [6.1 (1.2-30.7), 3.9 (1.2-30.2), and 4.9 (1.4-17.0) respectively] abnormal NCS findings after adjustment for age, gender and the presence of DM. CONCLUSION: The study revealed that over half of the patients with CTS had NCS/ Electromyography (EMG) abnormalities. Presence of hand muscles weakness, positive Phalen and Tinel's signs predict abnormal findings on NCS/EMG in patients with CTS.

Effect of stevia aqueous extract on the antidiabetic activity of saxagliptin in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Stevia rebaudiana Bertoni is a perennial herb that belongs to the Asteraceae family. It is a natural sweetener plant known as "Sweet Leaf", "Sweet Herbs" and "Honey Leaf", which is estimated to be 300 times more sweetening than sugar cane. Stevia has been used as a traditional treatment for diabetes in many countries for hundreds of years. Several animal studies referred to the antihyperglycemic activity of stevia. However, the combined use of stevia with saxagliptin has not been studied so far, so this study has been done. The aim of the present study was to evaluate the antihyperglycemic effect of stevia alone and in combination with saxagliptin. MATERIALS AND METHODS: Diabetes was induced in rats by i.p. injection of streptozotocin and nicotinamide. Animals were divided into five groups, each contains eight rats. Group I: included negative controland group II: included diabetic control that received saline. Group III: included diabetic rats that received 400 mg/kg/day stevia aqueous extract. Group IV: included diabetic rats that received saxagliptin 10 mg/kg/day. Group V: included diabetic rats that received stevia 400 mg/kg + saxagliptin 10 mg/kg. Food and water intake were measured daily while body weight was measured weekly. After 3 weeks animals were sacrificed and blood and tissue samples were collected. Fasting blood glucose (FBG), serum insulin, serum dipeptidylepeptidase-4 (DPP-4), TC, TGs, LDL, HDL, GSH and MDA were measured in treated and control rats by colorimetric and ELISA methods. RESULTS: Both stevia and saxagliptin significantly reduced food, water intake, body weight and FBG. Stevia with saxagliptin produced more significant decrease in FBG. While serum insulin increased significantly in stevia, saxagliptin treated groups and their combination. Serum DPP-4 decreased significantly in all treated groups, concerning lipid profile, stevia and saxagliptin notably lowered TC, TGs, and LDL and increased HDL. Both stevia and saxagliptin remarkably decreased MDA and increased GSH compared to diabetic rats. In addition, stevia significantly improved the antidiabetic effects of saxagliptin. CONCLUSION: Stevia has an antihyperglycemic effect and could enhance the antidiabetic activity of saxagliptin. DPP-4 attenuation, antihyperlipidemic and antioxidant activity as well as improvement of insulin sensitivity may be involved in the antidiabetic action of stevia.

Loss of miR-101-3p Promotes Transmigration of Metastatic Breast Cancer Cells through the Brain Endothelium by Inducing COX-2/MMP1 Signaling.

Brain metastases represent one of the incurable end stages in breast cancer (BC). Developing effective or preventive treatments is hampered by a lack of knowledge on the molecular mechanisms driving brain metastasis. Transmigration of BC cells through the brain endothelium is a key event in the pathogenesis of brain metastasis. In this study, we identified miR-101-3p as a critical micro-RNA able to reduce transmigration of BC cells through the brain endothelium. Our results revealed that miR-101-3p expression is downregulated in brain metastatic BC cells compared to less invasive variants, and varies inversely compared to the brain metastatic propensity of BC cells. Using a loss-and-gain of function approach, we found that miR-101-3p downregulation increased transmigration of BC cells through the brain endothelium in vitro by inducing COX-2 expression in cancer cells, whereas ectopic restoration of miR-101-3p exerted a metastasis-reducing effect. In regulatory experiments, we found that miR-101-3p mediated its effect by modulating COX-2-MMP1 signaling capable of degrading the inter-endothelial junctions (claudin-5 and VE-cadherin), key components of the brain endothelium. These findings suggest that miR-101-3p plays a critical role in the transmigration of breast cancer cells through the brain endothelium by modulating the COX-2-MMP1 signaling and thus may serve as a therapeutic target that can be exploited to prevent or suppress brain metastasis in human breast cancer.

The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients.

The necessity for early detection and hence improving the outcome of treatment of hepatocellular carcinoma (HCC) is critical especially in Hepatitis C virus (HCV)-Genotype 4 induced cases. In our current work, we examined the miRNA-152 and DNMT-1 expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients as an attempt to evaluate the potential benefits of these new circulating, noninvasive, prognostic, epigenetic markers for liver cirrhosis and carcinogenesis of Egyptian patients. Eighty subjects were included in this study, divided into two groups; group I (40 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 18) and subgroup Ib (CLD with cirrhosis, n = 22), group II (CLD patients with HCC, n = 20), and control (Healthy volunteer, n = 20). The expression of miRNA-152 and DNMT-1 genes were analyzed using Real-Time PCR. MiRNA-152 showed a persistent and significant downregulation in all diseased groups, which was in consistence with the progression of the disease toward the HCC stage. DNMT-1 showed upregulation in all diseased groups when compared to control and subgroup Ia. The miRNA-152 was shown to correlate inversely with DNMT-1 in subgroup Ia, Ib and group II (r = -0.557, p < 0.01), (r = -0.850, p < 0.001) and (r = -0.544, p < 0.02) respectively. In addition, miRNA-152 and DNMT-1 showed a diagnostic ability to discriminate between cases of cirrhosis and HCC against CLD without cirrhosis (p < 0.01), while DNMT-1 did not, except between HCC and cirrhotic cases. Furthermore, both genes can be considered as predictor and prognostic parameters for cirrhosis (OR = 1.041, p = 0.043) and (OR = 1.039, p = 0.04) respectively, while miRNA-152 alone is proved as a prognostic marker for HCC (OR = 1.003, p = 0.044). Finally, the persistent reverse correlation between miRNA-152 with DNMT-1 prompts their use as noninvasive prognostic biomarkers for HCV induced liver cirrhosis and HCC in HCV Genotype 4 patients.

Comparative metabolomics of MCF-7 breast cancer cells using different extraction solvents assessed by mass spectroscopy.

Metabolic profiling of cancer cells can play a vital role in revealing the molecular bases of cancer development and progression. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was employed for the determination of signatures found in ER+/PR+ breast cancer cells derived from MCF-7 using different extraction solvents including: A, formic acid in water; B, ammonium hydroxide in water; C, ethyl acetate; D, methanol: water (1:1, v/v); and E, acetonitrile: water (1:1, v/v). The greatest extraction rate and diversity of metabolites occurs with extraction solvents A and E. Extraction solvent D showed moderate extraction efficiency, whereas extraction solvent B and C showed inferior metabolite diversity. Metabolite set enrichment analysis (MSEA) results showed energy production pathways to be key in MCF-7 cell lines. This study showed that mass spectrometry could identify key metabolites associated with cancers. The highest enriched pathways were related to energy production as well as Warburg effect pathways, which may shed light on how energy metabolism has been hijacked to encourage tumour progression and eventually metastasis in breast cancer.

A case of rifampicin-induced haemolysis.

We present a case of pulmonary tuberculosis treated with a rifampicin (RMP) containing regimen, which led to marked haemolysis and acute kidney injury. The patient was shown to have RMP-induced haemolysis on detailed immunological testing. RMP is described as a rare cause of drug-induced haemolysis in the literature. However, it is a widely used drug and this complication may be severe. RMP-induced haemolysis precludes further treatment with the drug. Clinicians should consider this possibility and seek advice if patients on RMP develop haemolysis.

Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Decellularized matrices of biologic tissue have performed well as wound care dressings. Extracellular matrix-based dressings are subject to rapid degradation by excessive protease activity at the wound environment. Stabilized, acellular, equine pericardial collagen matrix (sPCM) wound care dressing is flexible cross-linked proteolytic enzyme degradation resistant. sPCM was structurally characterized utilizing scanning electron and atomic force microscopy. In murine excisional wounds, sPCM was effective in mounting an acute inflammatory response. Postwound inflammation resolved rapidly, as indicated by elevated levels of IL-10, arginase-1, and VEGF, and lowering of IL-1ß and TNF-α. sPCM induced antimicrobial proteins S100A9 and ß-defensin-1 in keratinocytes. Adherence of Pseudomonas aeruginosa and Staphylococcus aureus on sPCM pre-exposed to host immune cells in vivo was inhibited. Excisional wounds dressed with sPCM showed complete closure at d 14, while control wounds remained open. sPCM accelerated wound re-epithelialization. sPCM not only accelerated wound closure but also improved the quality of healing by increased collagen deposition and maturation. Thus, sPCM is capable of presenting scaffold functionality during the course of wound healing. In addition to inducing endogenous antimicrobial defense systems, the dressing itself has properties that minimize biofilm formation. It mounts robust inflammation, a process that rapidly resolves, making way for wound healing to advance.-El Masry, M. S., Chaffee, S., Das Ghatak, P., Mathew-Steiner, S. S., Das, A., Higuita-Castro, N., Roy, S., Anani, R. A., Sen, C. K. Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Psychometric Properties of an Arabic Pain Anxiety Symptoms Scale-20 (PASS-20) in Healthy Volunteers and Patients Attending a Physiotherapy Clinic.

PURPOSE: The aim of this study was to cross-culturally adapt the PASS-20 questionnaire for use in Libya. METHODS: Participants were 71 patients (42 women) attending the physiotherapy clinic, Ibn Sina Hospital, Sirt, Libya for management of persistent pain and 137 healthy unpaid undergraduate students (52 women) from the University of Sirt, Libya. The English PASS-20 was translated into Arabic. Patients completed the Arabic PASS-20 and the Arabic Pain Rating Scales on two occasions separated by a 14-day interval. Healthy participants completed the Arabic PASS-20 on one occasion. RESULTS: The internal consistency (ICC) for pain patient and healthy participant samples yielded a good reliability for the total score, cognitive anxiety, fear of pain, and physiological anxiety. The test-retest reliability of the Arabic PASS-20 score showed high reliability for the total score (ICC = 0.93, p < 0.001), escape/avoidance (ICC = 0.93, p < 0.001), fear of pain (ICC = 0.94, p < 0.001), and physiological anxiety subscales (ICC = 0.96, p < 0.001) and good reliability for the cognitive anxiety (ICC = 0.85, p < 0.001). Inspection of the Promax rotation showed that each factor comprised of five items were consistent with the theoretical constructs of the original PASS-20 subscales. CONCLUSION: The Arabic PASS-20 retained internal consistency and reliability with the original English version and can be used to measure pain anxiety symptoms in both pain and healthy individual samples in Libya.

Modulation of DNA damage response and induction of apoptosis mediates synergism between doxorubicin and a new imidazopyridine derivative in breast and lung cancer cells.

DNA damage response machinery (DDR) is an attractive target of cancer therapy. Modulation of DDR network may alter the response of cancer cells to DNA damaging anticancer drugs such as doxorubicin. The aim of the present study is to investigate the effects of a newly developed imidazopyridine (IAZP) derivative on the DDR after induction of DNA damage in cancer cells by doxorubicin. Cytotoxicity sulphrhodamine-B assay showed a weak anti-proliferative effect of IAZP alone on six cancer cell lines (MCF7, A549, A549DOX11, HepG2, HeLa and M8) and a normal fibroblast strain. Combination of IAZP with doxorubicin resulted in synergism in lung (A549) and breast (MCF7) cancer cells but neither in the other cancer cell lines nor in normal fibroblasts. Molecular studies revealed that synergism is mediated by modulation of DNA damage response and induction of apoptosis. Using constant-field gel electrophoresis and immunofluorescence detection of γ-H2AX foci, IAZP was shown to inhibit the repair of doxorubicin-induced DNA damage in A549 and MCF7 cells. Immunoblot analysis showed that IAZP suppresses the phosphorylation of the ataxia lelangiectasia and Rad3 related (ATR) protein, which is an important player in the response of cancer cells to chemotherapy-induced DNA damage. Moreover, IAZP augmented the doxorubicin-induced degradation of p21, activation of p53, CDK2, caspase 3/7 and phosphorylation of Rb protein. These effects enhanced doxorubicin-induced apoptosis in both cell lines. Our results indicate that IAZP is a promising agent that may enhance the cytotoxic effects of doxorubicin on some cancer cells through targeting the DDR. It is a preliminary step toward the clinical application of IAZP in combination with anticancer drugs and opens the avenue for the development of compounds targeting the DDR pathway that might improve the therapeutic index of anticancer drugs and enhance their cure rate.

Epigenetics and miRNA as predictive markers and targets for lung cancer chemotherapy.

Lung cancer cells show inherent and acquired resistance to chemotherapy. The lack of good predictive markers/novel targets and the incomplete understanding of the mechanisms of resistance limit the success of lung cancer response to chemotherapy. In the present study, we used an isogenic pair of lung adenocarcinoma cell lines; A549 (wild-type) and A549DOX11 (doxorubicin resistant) to study the role of epigenetics and miRNA in resistance/response of non-small cell lung cancer (NSCLC) cells to doxorubicin. Our results demonstrate differential expression of epigenetic markers whereby the level of HDACs 1, 2, 3 and4, DNA methyltransferase, acetylated H2B and acetylated H3 were lower in A549DOX11 compared to A549 cells. Fourteen miRNAs were dys-regulated in A549DOX11 cells compared to A549 cells, of these 14 miRNAs, 4 (has-mir-1973, 494, 4286 and 29b-3p) have shown 2.99 - 4.44 fold increase in their expression. This was associated with reduced apoptosis and higher resistance of A549DOX11cells to doxorubicin and etoposide. Sequential treatment with the epigenetic modifiers trichostatin A or 5-aza-2'-deoxycytidine followed by doxorubicin resulted in: (i) enhanced sensitivity of both cell lines to doxorubicin especially at low concentrations, (ii) enhanced doxorubicin-induced DNA damage in both cell lines, (iii) dysregulation of some miRNAs in A549 cells. In conclusion, A549DOX11 cells resistant to DNA damaging drugs have epigenetic profile and miRNA expression different from the sensitive cells. Moreover, epigenetic modifiers may reverse the resistance of certain NSCLC cells to DNA damaging agents by enhancing induction of DNA damage. This may open the door for using epigenetic profile/miRNA expression of some cancer cells as resistance markers/targets to improve response of resistant cells to doxorubicin and for the use of combination doxorubicin/epigenetic modifiers to reduce doxorubicin toxicity.

Pathological features and prognosis of lobular carcinoma in Egyptian breast cancer patients.

AIM: To illustrate the differences between invasive lobular and ductal carcinomas (ILCs and IDCs) in terms of baseline demographics, pathologic features and recurrence in Egyptian breast cancer patients. PATIENTS & METHODS: Retrospective analysis of breast cancer patients diagnosed and treated between 2000 and 2008 was performed. RESULTS: 176 (8.5%) and 1758 (85%) cases were diagnosed with ILC and IDC, respectively. Compared with IDC, ILC was less observed in patients under 35 years of age (3.4 vs 9.3%; p = 0.009), and was associated with more bilaterality (p = 0.001), advanced tumor stage (p = 0.027) and nodal involvement (p = 0.004). On the other hand, IDC was significantly associated with more luminal B-like phenotype (16.9 vs 8.1%; p < 0.001) and more HER2-enriched disease (11.5 vs 2.7%; p < 0.001). At a median follow-up time of 64 months, ILC histology was independently associated with better disease-free survival (hazard ratio: 0.58; 95% CI: 0.36-0.93; p = 0.023). Bone and peritoneal relapses were more common in ILC, while lung relapses were more common in IDC. CONCLUSION: ILC has distinct biologic and prognostic features that may warrant different therapeutic approaches.

Midsagittal anatomy of lumbar lordosis in adult egyptians: MRI study.

Despite the increasing recognition of the functional and clinical importance of lumbar lordosis, little is known about its description, particularly in Egypt. At the same time, magnetic resonance imaging (MRI) has been introduced as a noninvasive diagnostic technique. The aim of this study was to investigate the anatomy of the lumbar lordosis using midsagittal MRIs. Normal lumbar spine MRIs obtained from 93 individuals (46 males, 47 females; 25-57 years old) were evaluated retrospectively. The lumbar spine curvature and its segments "vertebrae and discs" were described and measured. The lumbar lordosis angle (LLA) was larger in females than in males. Its mean values increased by age. The lumbar height (LH) was longer in males than in females. At the same time, the lumbar breadth (LB) was higher in females than in males. Lumbar index (LI = LB/LH × 100) showed significant gender differences (P < 0.0001). Lordosis was formed by wedging of intervertebral discs and bodies of lower lumbar vertebrae. In conclusion, MRI might clearly reveal the anatomy of the lumbar lordosis. Use of LI in association with LLA could be useful in evaluation of lumbar lordosis.

Monocyte adhesion molecules expression in patients with chronic hepatitis C liver disease.

BACKGROUND: Chronic viral hepatitis is histologically characterized by predominantly periportal infiltration of mononuclear cells, including lymphocytes and monocytes/macrophages. Intralobular infiltration of these inflammatory cells is an ominous sign of deterioration and a criterion for disease activity. OBJECTIVE: To assess the monocyte inflammatory milieu, monocytes adhesion molecules, their endothelial receptors, cytokines and chemokines in patients with HCV induced chronic liver disease, in an attempt to clarify the role of blood monocytes in induction of inflammation and fibrogenesis in chronic hepatitis C liver disease. SUBJECTS AND METHODS: The current study included 60 patients with chronic liver disease categorized into 2groups: Patients chronic hepatitis C (CHC) and patients with liver cirrhosis (LC), 15 patients each; 15 healthy subjects were included as normal controls. Immunophenotype characterization was carried out by flowcytometric analysis for identification of CD11a, CD11b and CD49d monocyte surface antigen expression in different groups studied. The circulating levels of the soluble adhesion molecules (sE-selectin, sICAM-1 and sVCAM-1), cytokines (TNF-α and IL-1) and chemokines (MCP-1) were also assessed by immunoassays. RESULTS: Data demonstrated a significant increase (p<0.01) in the surface expression of CD11a on peripheral blood monocytes and in the circulating levels sE-selectins, sICAM-1, sVCAM-1 and TNF-α in both groups of patients compared to healthy subjects. Data also revealed a significant increase (p<0.01) in the surface expression of each of CD11b and CD49d on peripheral blood monocytes and in the circulating levels sICAM-1, sVCAM-1 and TNF-α in patients with LC compared to those with CHC. Moreover, data demonstrated that the increase in surface antigen expression of each CD11a (p<0.01), CD11b (p<0.05) and CD49d (p<0.01) on circulating peripheral blood monocytes is positively correlated with the increase in the circulating levels of each of sICAM-1 and sVCAM-1 in the both groups of patients. CONCLUSIONS: These findings suggest that the modulation of monocyte-subset recruitment into the liver via adhesion molecules or cytokines/cytokine receptors may represent promising approaches for therapeutic interventions in human liver fibrosis. Measurement of serum soluble adhesion molecules may be useful for monitoring progression of liver inflammation and fibrosis during CHC.

Environmental risks of insecticides cholinesterase inhibitors.

This study conducted on 423 inhabitant (372 adults and 51 children) blood samples were collected from patients hosted in the Emergency Hospital of Mansoura University. The clinical diagnosis of such patients was acute insecticides poisoning. The aim of the present study is to study patients with cholinesterase (ChE) inhibitor organophosphorus insecticides intoxication from the laboratory point of view. The plasma samples were analyzed for levels of ChE enzyme and acetyl cholinesterase enzyme activity by spectrophotometer. The pesticides were identified using Gas Chromatography-Electron Captured Detector (GC-ECD). The results of GC-ECD instrument of all patients revealed that parathion (organophosphorous insecticide) poisoning was found in their blood samples. The mode of poisoning was accidentally by inhalation and skin contact. The poisoning cases of children were of mild poisoning. The degrees of poisoning of adults were severe in 138, moderate in 201 and mild in 33 cases. In conclusion, results of the present study revealed that the widely used insecticides in Dakahlyia governorate are the organophosphorous insecticides specifically parathion insecticide.