Biomedical subjects

Mahmoud Huleihel

Publications and source records attributed to Mahmoud Huleihel.

48 records · Page 3Linked to original sources

PubMed2002

Molecular and cellular interface between behavior and acute coronary syndromes.

This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L-CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients.

Acute Disease↗

PubMed2002

Metabolic pathways of N-methanocarbathymidine, a novel antiviral agent, in native and herpes simplex virus type 1 infected Vero cells.

N-methanocarbathymidine ((N)-MCT), a thymidine analog incorporating a pseudosugar with a fixed Northern conformation, exhibits potent antiherpetic activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). This study contrasts the metabolic pathway of (N)-MCT and the well-known antiherpetic agent ganciclovir (GCV) in HSV-1-infected and uninfected Vero cells. Treatment of HSV-1 infected Vero cells immediately after viral infection with (N)-MCT profoundly inhibited the development of HSV-1 infection. Using standard plaque reduction assay to measure viral infection, (N)-MCT showed a potency greater than that of ganciclovir (GCV), the IC50s were 0.02 and 0.25 microM for (N)-MCT and GCV, respectively. (N)-MCT showed no cytotoxic effect on uninfected Vero cells (CC50>100 microM). Dose and time dependence studies showed high levels of (N)-MCT-triphosphate ((N)-MCT-TP), and GCV-triphosphate (GCV-TP) in HSV-1-infected cells incubated with (N)-MCT or GCV, respectively. In contrast, uninfected cells incubated with (N)-MCT showed elevated levels of (N)-MCT-monophosphate only, while low levels of mono, di- and triphosphates of GCV were found following incubation with GCV. Although the accumulation rate of (N)-MCT and GCV phosphates in HSV-1-infected cells were similar, the decay rate of (N)-MCT-TP was slower than that of GCV-TP. These results suggest that: (1) the antiviral activity of (N)-MCT against herpes viruses is mediated through its triphosphate metabolite; (2) in contrast to GCV, the diphosphorylation of (N)-MCT in HSV-1- infected cells is the rate limiting step; (3) (N)-MCT-TP accumulates rapidly and has a long half-life in HSV-1-infected cells; and (4) HSV-tk catalyzed the mono, and diphosphorylation of (N)-MCT while monophosphorylating GCV only. These results provide a biochemical rational for the highly selective and effective inhibition of HSV-1 by (N)-MCT.

Animals↗

PubMed2002

IL-1 activity is expressed differently during pregnancy in the rat uterine artery than in aortic or uterine tissues.

PROBLEM: Uterine artery was shown to be unique in its capacity to change in size and function during pregnancy. As interleukin-1 (IL-1) was shown to be involved in reproduction processes, the aim of this study was to determine the levels of IL-1 activity of the uterine artery tissue in pregnant rat. METHOD OF STUDY: Nine virgins and nine midpregnant rats were selected. Both uterine arteries were obtained, together with reference tissues from aorta and uterus. The levels of IL-I were examined in the above tissues after culturing with media alone (control; CT), and media that contained stimulants like tumor necrosis factor-alpha (TNF-a) or lipopolysaccharide (LPS). IL-1-like activity was evaluated by its capacity to promote the culture growth of 1A-5 and cytotoxic T lymphocyte derived (CTLD) cell lines. This activity was expressed as optical density (OD)/mg protein of the examined organ. RESULTS: Uterine artery tissue, of pregnant rats, cultured in medium alone produced significantly higher levels of IL-1 than uterine artery of virgin animals under the same conditions (16.2 S.E. 1.3 versus 0.6 S.E. 0.05 OD/mg protein, respectively; P < 0.02). Stimulation of uterine artery in vitro by LPS and TNF increased their capacity to secrete IL-1. In comparison with uterine artery, aorta produced higher levels of IL-1 in virgin rats compared with pregnant rats (13.6 S.E. 1.2 versus 1.6 S.E. 0.1; P < 0.02). Stimulation of aorta tissues (from both virgin and pregnant rats) with LPS, in vitro, significantly decreased their capacity to secrete IL-1 (P < 0.04). Stimulation of aorta tissues from virgin rats with TNF-alpha, in vitro, did not change their capacity to secrete IL-1 activity. However, stimulation of aorta tissues from pregnant rats with TNF-alpha decreased the secretion of bioactive IL-1. The levels of IL-1 produced by uterine tissues from virgin and pregnant rats were similar, and stimulation with either LPS or TNF-alpha significantly decreased their capacity to secrete IL-1 (P < 0.04). CONCLUSIONS: The high level of IL-1 activity detected during pregnancy in the uterine artery may suggest its unique involvement in the changes occurring throughout pregnancy in those blood vessels.

Animals↗

PubMed2002

Induction of transferrin secretion in murine Sertoli cells by FSH and IL-1: the possibility of different mechanism(s) of regulation.

In the present study we examined the capacity of interleukin-1 (IL-1) alpha, beta, interleukin-1 receptor antagonist (IL-1ra) and follicle stimulating hormone (FSH) to induce transferrin secretion by Sertoli cells under in vitro conditions. Primary Sertoli cell (SC) cultures from immature mice secreted constitutively transferrin. Stimulation of these cultures with IL-1alpha, IL-1beta significantly increas\d their capacity to secrete transferrin. Addition of IL-1ra to unstimulated SC cultures did not affect their capacity to secrete transferrin. Stimulation of SC cultures with a combination of both IL-1alpha and FSH or IL-1beta and FSH showed additive effect between IL-1 and FSH in their capacity to induce transferrin secretion by these cells. However, stimulation of Sertoli cells with a combination of both IL-1ra and FSH did not affect their capacity to secrete transferrin compared with FSH-stimulated cultures. Our results may suggest the involvement of testicular paracrine/autocrine factors (IL-1) and endocrine (FSH) factors in the regulation of transferrin secretion by SC. This capacity seems to be differently regulated by these factors. Thus, IL-1alpha and beta may directly affect physiological functions of the testis; which may suggest their involvement in the regulation of spermatogenesis and spermiogenesis processes and male fertility.

Animals↗

PubMed2002

Spectroscopic characterization of human and mouse primary cells, cell lines and malignant cells.

Fourier transform infrared (FTIR) spectroscopy is currently being developed as a new optical approach to the diagnosis and characterization of cell or tissue pathology. The advantage of FTIR microspectroscopy over conventional FTIR spectroscopy in the diagnosis of malignancies is that it facilitates inspection of restricted regions of the cell culture or tissue. In this study, we set out to evaluate FTIR microspectroscopy as a diagnostic tool for identifying retrovirus-induced malignancies. Our study showed significant and consistent differences between cultures of different types of cells of both mouse and human origin, i.e. primary fibroblast cells (one to two passages in cell culture), fibroblast cell lines and malignant cells transformed by murine sarcoma virus. An impressive decrease in the levels of phosphate and other metabolites was seen in malignant cells compared with primary cells. The levels of these metabolites in the cell lines were significantly lower than in the primary cells but higher than in the malignant cells. In addition, the peak attributed to the PO2- symmetric stretching mode at 1082 cm(-1) in primary cells shifted significantly to 1085 cm(-1) for the cell line and to 1087 cm(-1) for the malignant cells. These differences taken together with differences in the shapes of various bands throughout the spectrum strongly support the possibility of developing FTIR microspectroscopy for the detection and study of malignant--and possibly premalignant--cells.

Animals↗

PubMed2002

Anti-herpes simplex virus effect of an aqueous extract of propolis.

BACKGROUND: Propolis, a natural product from beehives, comprises a complex of chemicals, the most important group being flavinoids, which play a role in antiviral protection. OBJECTIVES: To test the inhibitory effect of propolis extract against herpes simplex viruses in vitro and in vivo. METHODS: In vitro: propolis was added to Vero cells at various times and concentrations before, at or after infection with HSV-1. In vivo: the effect of propolis was tested in newborn rats infected s.c. or i.p. and on rabbit come as infected with HSV-1. RESULTS: In vitro: 0.5% propolis extract caused 50% inhibition of HSV infection. There was indirect evidence for a strong interaction between the propolis extract and the surface of the Vero cells, but there was no direct interaction with HSV-1 particles. Administration of propolis before or at the time of infection yielded the most significant inhibitory effect, but even when 10% propolis extract was added 2 hours post-infection it gave 80-85% protection. In vivo: as little as 5% propolis prevented the appearance and development of symptoms of local and i.p. HSV-1 infection in rats and of corneal HSV-1 infection in rabbits. There were no cytotoxic effects at a concentration of 10% in vitro or 20% in vivo. CONCLUSIONS: The potent antiviral activity of propolis against HSV-1 infection in vitro and In vivo is probably due to prevention of virus absorption into the host cells and/or inhibition of an internal step(s) during the viral replication cycle.

Animals↗

PubMed2002

Intravenous magnesium sulphate effect on maternal serum and amniotic fluid cytokines levels in preterm labour patients.

Our objective was to evaluate the effect of intravenous magnesium sulphate administration to patients with preterm labour on maternal serum and amniotic fluid IL-1beta, IL-6, IL-10 and TNFalpha concentrations. Thirty-six patients at 24-34 weeks of singleton gestation, who presented with contractions (> or = 8 in 60 min) had amniocentesis to rule out intrauterine infection. The patients received intravenous MgSO4 for tocolysis. Twenty-six patients had amniocentesis performed before initiation of MgSO4 (controls) while 10 others had the procedure during tocolytic therapy (study patients). Magnesium, IL-1beta, IL-6, TNFalpha and IL-10 concentrations were measured. Study and control groups were statistically compared using Student t test. Mean magnesium levels were significantly higher in the study group (P < 0.01). There were no significant differences between the cytokines levels in maternal serum and in amniotic fluid between the groups. Our results suggest that the mechanism of magnesium as a tocolytic agent may not be mediated via the examined cytokines.

Adult↗

PubMedDate not supplied

Use of Fourier transform infrared microscopy for the evaluation of drug efficiency.

Fourier transform infrared (FTIR) spectroscopy has been used by chemists as a powerful tool to characterize inorganic and organic compounds. In this study, we examine the potential of FTIR microspectroscopy for early evaluation of therapy efficiency. For this purpose, we examine the effect of acyclovir (a known antiherpetic drug) on the development of herpes simplex virus type 1 (HSV-1) infection in cell culture. Also, we examine spectral changes in lymphocytes obtained from leukemia patients after appropriate chemotherapy treatment. Our results show early and significant spectral indicators for successful infection of Vero cells with HSV-1. Treatment of these infected cells with increasing doses of acyclovir reduces clearly the spectral changes caused by the infection in a correlation with inhibiting the development of the cytopathic effect (CPE) induced by this virus. Also significant and consistent spectral differences between lymphocytes from human leukemia patients compared to that from healthy persons are obtained. Treatment of these leukemia patients with appropriate drugs reduces significantly these spectral differences in a correlation with the improvement of the patient's clinical situation. It seems that FTIR spectroscopy can be used as an effective tool for early evaluation of the efficiency of drugs.

Acyclovir↗

PubMedDate not supplied

Maternal hypoxia during pregnancy delays the development of motor reflexes in newborn mice.

Prenatal hypoxic-ischemic brain injury is believed to cause permanent neurological deficits in newborns. We investigated the possibility that maternal hypoxia during pregnancy leads to offspring brain damage and its prevention by i.p. administration of MgSO4. Pregnant mice at gestation day 17 were exposed to hypoxia or air following pretreatment with saline or Mg. Newborn mice to mothers exposed to hypoxia demonstrated faster development of morphogenic parameters such as eyelid opening, hair growth and teeth eruption. In addition, hypoxia delayed the development of motor reflexes. Pretreatment with Mg compensates for hypoxia-induced impairment and in some cases accelerates the development of these functions. In conclusion, maternal hypoxia significantly modifies the developmental process of newborn mice. In our study, pretreatment with Mg showed significant prophylactic action against motor impairments.

Animals↗

PubMedDate not supplied

Over expression of interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist in testicular tissues from sexually immature mice as compared to adult mice.

The levels of IL-1alpha, IL-1beta and IL-1Ra were higher in homogenates of testicular tissue from sexually immature than those from mature mice. Immunohistochemical staining of testicular tissues from sexually immature and adult mice show that differentiated germ cells express higher levels of IL-1alpha compared to Sertoli cells and Leydig cells/interstitial cells. Peritubular cells of sexually immature and adult mice did not express IL-1alpha. Testicular tissue cells of adult mice showed high levels of expression of IL-1beta, mainly in the cytoplasm and nucleus of the spermatogonia and in spermatocytes. Sertoli cells and Leydig/interstitial cells were also highly stained for IL-1beta. However, peritubular cells did not express IL-1beta. On the other hand, testicular tissue cells from sexually immature mice, showed high levels of IL-1beta, mainly in spermatocytes. Spermatogonia showed low levels of IL-1beta expression. Also, high levels of IL-1beta expression were detected in Leydig/interstitial cells. Peritubular cells clearly showed IL-1beta expression. Testicular tissue cells from adult mice, showed IL-1Ra expression in spermatogonia, Sertoli and Leydig/interstitial cells. IL-1Ra expression was clearly present in the Golgi apparatus of spermatogonia and Sertoli cells. However, peritubular cells did not show IL-1Ra expression. Testicular tissue cells from sexually immature mice, also showed high levels of IL-1Ra expression mainly in the cytoplasm and nucleus of the spermatogonia and Sertoli cells. In addition, Leydig/interstitial cells and peritubular cells also expressed IL-1Ra. Our results demonstrate, for the first time, the expression of IL-1beta in germ and Sertoli cells, and IL-1Ra in Leydig/interstitial cells of testicular tissues from adult and sexually immature mice, under in vivo conditions. In addition, the relative elevated levels of the IL-1 system in the testis of immature mice compared to mature mice may indicate its involvement in the spermatogenesis.

Animals↗

PubMedDate not supplied

Perfusion of human term placentas with lipopolysaccharide did not affect the capacity of the fetal and maternal tissues to produce interleukin-10.

IL-10 is anti-inflammatory cytokine that is involved in the regulation of the pregnancy process. We examined the capacity of fetal and maternal placental tissues from human term placentas, to produce IL-10, in the presence and absence of LPS. The levels of IL-10 were examined (by ELISA and immunohistochemical staining) in the fetal and maternal tissues of human placentas after 10 hours of perfusion, in the presence or absence of lipopolysaccharide (LPS; 1 microg/k"g perfused tissue). We could detect IL-10 in amnion (A; 13.91+/-11.35 pg/ml) and chorion (CH; 7.85 +/- 6.38 pg/ml) tissue homogenates, and in the homogenates of three different sites of the placental tissue compartment (subchorionic placenta (SubCH); 7.39 +/- 4.39 pg/ml, mid-placenta (MidPL); 8.9 +/- 4.73 pg/ml and decidua (Decid); 16.48 + 11.86 pg/ml). Immunohistochemical studies showed that IL-10 was localized in the epithelial cells of the amnion, and in the fibroblasts and macrophages of the chorion. In the placenta and mid-placental sites, IL-10 is localized mainly in cytotrophoblasts and syncytotrophoblasts. The presence of LPS in the perfusion media of the placentas for 10 hours, did not significantly affect the capacity of the fetal and maternal tissues to produce IL-10. Thus, our results may indicate the involvement of the fetal compartment in the down-regulation of the cell-mediated response of the maternal compartment against the fetus, by producing IL-10 under physiological conditions. Infection/inflammation agents such as LPS did not affect the expression levels of IL-10 in the placenta.

Female↗

PubMedDate not supplied

Lipopolysaccharide induces the expression of interleukin-1alpha distinctly in different compartments of term and preterm human placentae.

The aim of the study was to investigate the stimulatory effect of lipopolysaccharide (LPS) on IL-lalpha production in different compartments of term and preterm placental tissues. Homogenates from amnion, chorion, and from fetal (subchorionic placental tissues, maternal decidua, and mid-placental tissue before and after perfusion of isolated placental cotyledons of 5 term placentas and 4 placentas obtained after preterm birth (28-34 W of gestation) were examined. Isolated placental cotyledons were dually perfused LPS (100 ng/kg perfused placental tissue) was perfused into the maternal side during 10 hours. Homogenates of the samples were examined by ELISA for IL-1alpha levels, and paraffin sections of the samples were stained by immunohistochemical staining, to characterize the cellular origin of placental IL-1alpha. Paired t test and ANOVA determined statistical significance. In the homogenates, there was a tendency towards higher IL-lalpha levels in all preterm placental compartments as compared to the term compartments before perfusion. A significant increase was observed only in the chorion compartment (p = 0.035). LPS had significantly increased IL-la levels only in the decidua compartment of term placentas as compared to other placental compartments (p = 0.0004), and had decreased IL-1alpha levels in the mid-placenta (p = 0.034). In preterm placentas, addition of LPS did not affect the expression levels of IL-1alpha in either fetal or maternal compartments as determined by ELISA and immunohistochemical staining. IL-la levels in the chorion compartment of preterm placenta were significantly higher as compared to term placenta. LPS affects placental tissues of term and preterm placentas differently. Also, in the term placentas, LPS affected the different compartments differently. Thus, IL-1alpha may have a key role (as a autocrine/paracrine factor) in the regulation of normal and pathological pregnancy and parturition.

Autocrine Communication↗