Biomedical subjects

Mahmoud Huleihel

Publications and source records attributed to Mahmoud Huleihel.

At least 19 recordsLinked to original sources

PubMed2006

Perfusion with lipopolysaccharide differently affects the secretion of tumor necrosis factor-alpha and interleukin-6 by term and preterm human placenta.

This study has compared the functional capacity of term and preterm placentas in terms of production of pro-inflammatory cytokines in a perfusion system reflecting their ability to react to inflammatory agents, such as lipopolysaccharide (LPS), mimicking the situation of chorioamnionitis. We have demonstrated that term placentas secrete higher levels of tumor necrosis factor (TNF)-alpha compared with preterm placentas. Moreover, TNF-alpha secretion was significantly higher after exposure to LPS in the maternal and fetal sides of term placentas. In contrast, in preterm placentas, only the fetal side responded with a significant increase in secretion of TNF-alpha after exposure to LPS. The maternal side of term placentas secreted significantly higher amounts of interleukin (IL)-6 compared with preterm placentas. Exposure to LPS significantly decreased IL-6 secretion from the maternal side in both term and preterm placentas. Moreover, the fetal side of term placentas secreted significantly lower amounts of IL-6 compared with preterm placentas. In summary, this study has indicated that term and preterm placental tissues have a differing responsiveness to LPS stimulation, with term placentas disposed to a higher TNF-alpha:IL-6 ratio. Release of cytokines into fetal circulation is less than into the maternal side. However, TNF-alpha is released into fetal circulation after LPS stimulation and this may be relevant to the etiology of chorioamnionitis.

Enzyme-Linked Immunosorbent Assay↗

PubMed2006

Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial.

BACKGROUND: We aimed to examine the serum levels of inhibin A, vascular endothelial growth factor (VEGF), tumour necrosis factor alpha (TNFalpha), estradiol (E2) and progesterone levels after triggering of final oocyte maturation with GnRH agonist compared with HCG in patients with polycystic ovaries (PCO) and to investigate the relationship between these markers and ovarian hyperstimulation syndrome (OHSS). METHODS: Twenty-eight patients with PCO, undergoing controlled ovarian hyperstimulation with FSH and GnRH antagonist for IVF-embryo transfer treatment, were randomized for triggering of final oocyte maturation with GnRH agonist (GnRH agonist group, n = 15) or HCG (HCG group, n = 13). Blood samples were obtained on the day of randomization and thereafter every 2-7 days. Serum levels of inhibin A, VEGF, TNFalpha, E2 and progesterone, the incidence of OHSS, ovarian size and pelvic fluid accumulation were evaluated. RESULTS: Serum inhibin A, E2 and progesterone levels were significantly lower in the GnRH agonist group compared with the HCG group, particularly on the day of embryo transfer (P < 0.0001). Serum VEGF and TNFalpha levels were similar between the two groups. Four patients in the HCG group developed severe OHSS, whereas no patient had any symptoms or signs of OHSS in the GnRH-agonist group (P < 0.05). CONCLUSIONS: In patients with PCO treated with FSH/GnRH antagonist, final oocyte maturation with GnRH agonist instead of HCG reduces significantly inhibin A, E2 and progesterone levels during the luteal phase. This phenomenon reflects the inhibition of the corpus luteum function and may explain, at least in part, the mechanism of OHSS prevention in high-risk patients. Our results do not support a crucial role for VEGF or TNFalpha in OHSS.

Adult↗

PubMed2006

The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent models.

Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent models. Delayed development of sensory and motor reflexes during the first postnatal month of rodent life was observed by various groups. Impairment of motor function, learning and memory was evident in the adult animals. Activation of the signaling leading to cell death was detected as early as three hours following H/HI. An increase in the counts of apoptotic cells appeared approximately three days after the insult and peaked about seven days later. Around 14-20 days following the H/HI, the amount of cell death observed in the tissue returned to its basal levels and cell loss was apparent in the brain tissue. The study of the molecular mechanism leading to brain damage in animal models following prenatal hypoxia adds valuable insight to our knowledge of the central events that account for the morphological and functional outcomes. This understanding provides the starting point for the development and improvement of efficient treatment and intervention strategies.

Animals↗

PubMed2006

Induction of IL-1, in the testes of adult mice, following subcutaneous administration of turpentine.

PROBLEM: Interleukin-1 family is present in the testicular homogenates and its cellular compartments. It has been suggested that IL-1 is involved in physiological and pathological functions of the testicular tissues. In the present study we examined the effect of acute mostly localized inflammation, using turpentine, on the expression levels of testicular IL-1 system. METHODS OF STUDY: Mice were subcutaneously injected with steam-distilled turpentine or saline (control). Three hours to 10 days following the injection, mice were killed and testis and spleen were homogenized and examined for interleukin (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) levels by enzyme-linked immunosorbent assay and polymerase chain reaction. RESULTS: Subcutaneous injection of turpentine induced mice systemic inflammation, as indicated by significant increase in serum IL-1beta levels, and IL-1alpha, IL-1beta and IL-1ra in spleen homogenates. The levels of IL-1alpha, IL-1beta and IL-1ra were significantly induced in testicular homogenates of adult mice following subcutaneous injection of turpentine. The significant induction of testicular IL-1alpha was detected after 3-24 hr of turpentine injection and decreased later (after 3-10 days) to levels similar to the control. However, significant induction of testicular IL-1beta was detected only after 3-10 days of turpentine injection, and for testicular IL-1ra levels was detected after 3 hr to 6 days of turpentine injection, and after 10 days the levels were similar to the control. These results were also confirmed by mRNA expression of these factors. CONCLUSION: Our results demonstrate for the first time the distant effect of acute localized inflammation on testicular IL-1 levels. Thus, transient inflammatory response to infectious/inflammatory agents at non-testicular sites that elicit systemic IL-1 response should be considered during clinical treatment as a possible factor of male infertility.

Animals↗

PubMed2005

Different effects of magnesium sulfate and angiotensin II on the capacity of the fetal and maternal compartments of normal human placenta to secrete TNF-alpha and IL-6.

Three different protocols were carried out to evaluate the effect of magnesium sulfate (MgSO4) on the capacity of the normal human placenta to secrete TNF-alpha and IL-6 in presence and absence of angiotensin II (AII). Ten placentas were perfused with MgSO4 (6-7 mg%) or medium in the absence or presence of AII. Perfusate samples from fetal and maternal sites were collected and examined for IL-6 and TNF-alpha by ELISA. The maternal site of placentas exposed to AII showed only basal levels of TNF-alpha. Exposure of the placentas to MgSO4 resulted in significant increase in TNF-alpha and IL-6 in the maternal site (p < 0.05). However, the effect of MgSO4 was significantly attenuated by AII injected in presence of MgSO4. TNF-alpha and IL-6 levels in the maternal site significantly decreased (p < 0.05). The fetal site of the placentas exposed to MgSO4 or AII separately showed only basal levels of TNF-alpha and IL-6. However, TNF-alpha and IL-6 levels were significantly higher after injection of AII in the presence of MgSO4 compared to TNF-alpha levels in the fetal site of placentas exposed to AII alone (p < 0.05) or MgSO4 alone (p < 0.01). MgSO4 induced the ability of the placental maternal site to secrete TNF-alpha and IL-6. In the presence of both MgSO4 and AII, the effect of MgSO4 on the maternal site was significantly reduced. However, in the fetal site, MgSO4 alone had no significant effect on TNF-alpha and IL-6 levels although, in presence of AII and MgSO4, there was a significant increase in TNF-alpha and IL-6 levels. Elevation of TNF-alpha and IL-6 in the fetal compartment, which may affect fetal brain growth and development and placental function should be considered before administration of MgSO4 during pregnancy.

Angiotensin II↗

PubMed2005

Continuous monitoring of WBC (biochemistry) in an adult leukemia patient using advanced FTIR-spectroscopy.

Fourier transform infrared (FTIR)-spectroscopy has been found useful for monitoring the effectiveness of drugs during chemotherapy in leukemia patients. In the present work, spectral changes that occurred in the white blood cells (WBC) of an adult acute myeloid leukemia (AML) patient and their possible utilization for monitoring biochemistry of WBC were investigated. The phosphate absorbance from nucleic acids and the lipid-protein ratio in the WBC decreased immediately after treatment and then increased to levels of a control group. Similar observations were recorded in child patients with acute lymphoblastic leukemia (ALL) who were used as test cases. These parameters maybe used as possible markers to indicate successful remission and suggest that FTIR-spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a WBC population.

Adult↗

PubMed2005

Understanding how the herpes thymidine kinase orchestrates optimal sugar and nucleobase conformations to accommodate its substrate at the active site: a chemical approach.

The herpes virus thymidine kinase (HSV-tk) is a critical enzyme for the activation of anti-HSV nucleosides. However, a successful therapeutic outcome depends not only on the activity of this enzyme but also on the ability of the compound(s) to interact effectively with cellular kinases and with the target viral or cellular DNA polymerases. Herein, we describe the synthesis and study of two nucleoside analogues built on a conformationally locked bicyclo[3.1.0]hexane template designed to investigate the conformational preferences of HSV-tk for the 2'-deoxyribose ring. Intimately associated with the conformation of the 2'-deoxyribose ring is the value of the C-N torsion angle chi, which positions the nucleobase into two different domains (syn or anti). The often-conflicting sugar and nucleobase conformational parameters were studied using North and South methanocarbadeoxythymidine analogues (6 and 7), which forced HSV-tk to make a clear choice in the conformation of the substrate. The results provide new insights into the mechanism of action of this enzyme, which cannot be gleaned from a static X-ray crystal structure.

Antiviral Agents↗

PubMed2005

FTIR microscopy as a method for identification of bacterial and fungal infections.

Fourier-transform infrared (FTIR) microscopy is considered to be a comprehensive and sensitive method for detection of molecular changes in cells. The advantage of FTIR microspectroscopy over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of the examined sample. In the present study, we examined the potential of FTIR microscopy as an easy, rapid and reliable technique for discrimination between bacteria and fungi both of which are involved in various human and other animal infections. In many cases, there is no easy and rapid technique for identifying the cause of such infections whether it is bacteria, fungi or both. Knowing such information in a rapid way could be highly important for effective therapy. Our results proved detectable and significant spectral differences between bacterial and fungal samples. Representative peaks of bacteria and fungi appeared clearly in the spectra of a mixture of bacteria and fungi. It seems that this technique could be used for rapid discrimination between bacterial and fungal infections and contaminations.

Bacterial Infections↗

PubMed2005

Dynamics of the antiviral activity of N-methanocarbathymidine against herpes simplex virus type 1 in cell culture.

N-Methanocarbathymidine [(N)-MCT], a thymidine analogue, exhibits potent activity in cell culture against herpes simplex virus1 (HSV-1). (N)-MCT showed higher antiviral activity than ganciclovir (GCV). Continuous treatment of Vero cells with (N)-MCT immediately or 10 h post-infection (p.i.) fully prevented the development of viral infection. However, when infected cells were treated with (N)-MCT at 12 h p.i., there was only a partial inhibition (ca. 50%). Additionally, continuous treatment of infected cells with (N)-MCT for about 48 h was sufficient to achieve full prevention of viral infection without further treatment. These findings suggest the complete loss of herpes simplex thymidine kinase (HSV-tk) activity occurs after 48 h of treatment with (N)-MCT. This study helps to understand the mechanism and dynamics of antiHSV activity of (N)-MCT, which is necessary for its future development as an antiviral drug.

Animals↗

PubMed2005

Potent antiviral activity of north-methanocarbathymidine against Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) infection is a prerequisite for the development of Kaposi's sarcoma (KS). Blocking lytic KSHV replication may hinder KS tumorigenesis. Here, we report potent in vitro anti-KSHV activity of 2'-exo-methanocarbathymidine [North-methanocarbathymidine (N-MCT)], a thymidine analog with a pseudosugar ring locked in the northern conformation, which has previously been shown to block the replication of herpes simplex virus types 1 and 2. N-MCT inhibited KSHV virion production in lytically induced KSHV-infected BCBL-1 cells with a substantially lower 50% inhibitory concentration (IC50) than those of cidofovir (CDV) and ganciclovir (GCV) (IC50, mean +/- standard deviation: 0.08 +/- 0.03, 0.42 +/- 0.07, and 0.96 +/- 0.49 microM for N-MCT, CDV, and GCV, respectively). The reduction in KSHV virion production was accompanied by a corresponding decrease in KSHV DNA levels in the N-MCT-treated BCBL-1 cells, indicating that the compound blocked lytic KSHV DNA replication. A time- and dose-dependent accumulation of N-MCT-triphosphate (TP) was demonstrated in lytically induced BCBL-1 cells, while uninfected cells showed virtually no accumulation. The levels of N-MCT-TP were significantly decreased in the presence of 5'-ethynylthymidine, a potent inhibitor of herpesvirus thymidine kinase, resulting in the abrogation of anti-KSHV activity of N-MCT. N-MCT-TP more effectively blocked in vitro DNA synthesis by KSHV DNA polymerase with an IC50 of 6.24 +/- 0.08 microM (mean +/- standard deviation) compared to CDV-diphosphate (14.70 +/-2.47 microM) or GCV-TP (24.59 +/- 5.60 microM). Taken together, N-MCT is a highly potent and target-specific anti-KSHV agent which inhibits lytic KSHV DNA synthesis through its triphosphate metabolite produced in KSHV-infected cells expressing a virally encoded thymidine kinase.

Antiviral Agents↗

PubMed2005

Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis.

Zinc ions play an important role in testis development and spermatogenesis. Thus, nutritional zinc deficiency leads to aberrant testicular development, reduced spermatogenesis, and male sterility. The precise actions of zinc in mediating these functions and the mechanisms by which zinc is itself regulated in the testis, however, have not been adequately elucidated. We have assessed the distribution of the zinc-regulating proteins ZnT-1 and metallothionein I/II (MT I/II) in the mouse seminiferous tubule. Co-labeling for ZnT-1 and MT I/II demonstrated unique patterns of distribution for these proteins, with ZnT-1 present in Sertoli cells in addition to luminal spermatozoa and MT I/II restricted to spermatocytes. These findings were confirmed by dual-label immunofluorescence for ZnT-1 and the Sertoli cell marker, vimentin, and by immunoelectron microscopy. The differential expression patterns of ZnT-1 and MTs support the hypothesis that ZnT-1 and MTs play different roles in the regulation of intracellular zinc in this organ. The specific expression of ZnT-1 in the Sertoli cells, moreover, is consistent with their role in maintaining a nurturing, closely regulated environment for spermatogenesis.

Animals↗

PubMed2005

FTIR microscopy detection of cells infected with viruses.

Fourier-transform infrared (FTIR) microscopy is considered a comprehensive and sensitive method for detection of molecular changes in cells. The advantage of FTIR microspectroscopy over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of a cell culture or a tissue. We have shown that it is possible to apply FTIR microscopy as a sensitive and effective assay for the detection of cells infected with various members of the herpes family of viruses and retroviruses. Detectable and significant spectral differences between normal and infected cells were evident at early stages of the infection. Impressive changes in several spectroscopic parameters were seen in infected compared with uninfected cells. It seems that the change in spectral behavior is specific to the infecting virus, because cells infected with herpesviruses showed different spectral changes compared with cells infected with retroviruses.

Animals↗

PubMed2005

Interleukin-6 expression during normal maturation of the mouse testis.

In this study, we examined the cellular origin and the expression levels of interleukin-6 (IL-6) during normal maturation of mouse testis. The levels of IL-6 (protein and mRNA) were higher in testicular homogenates of sexually immature than mature mice. Immunohistochemical staining of testicular tissues of sexually immature and adult mice show that testicular germ cells, at different stages of differentiation, Leydig cells/interstitial cells and peritubular cells express IL-6. Our results demonstrate, for the first time, overexpression of IL-6 in testicular tissues of immature mice, as compared to mature mice, as well as the expression of IL-6 in germ cells of testicular tissues of adult and sexually immature mice. Thus, our results may indicate the involvement of the endocrine system (gonadotropins and testosterone) in the regulation of IL-6, which is involved in the regulation of testicular development, functions and spermatogenesis.

Animals↗

PubMed2005

Testicular interleukin-6 response to systemic inflammation.

Spermatogenesis is a highly controlled process of proliferation, meiosis, and differentiation. Systemic infection and chronic inflammation can impair testicular steroidogenesis and spermatogenesis. In this study, we examined the effect of systemic infection--intraperitoneal (i.p.) injection of lipopolysaccharide (LPS)--on the expression levels of IL-6 in the testis of sexually immature and adult mice. IL-6 levels in testicular homogenates of immature mice were significantly higher than in mature mice (both protein and RNA levels), before and after LPS injection. Injection of LPS (i.p.) into mature mice over 3 hours, significantly increased testicular IL-6 protein and mRNA levels (as demonstrated by ELISA and RT-PCR respectively) compared to the control group. Injection of LPS over 24 hours significantly increased IL-6 mRNA expression, but it did not significantly affect IL-6 protein levels in the homogenates. In contrast, stimulation of immature mice with LPS (2, 20 or 100 microg/mL) over 3 hours or LPS (2 or 20 microg/mL) over 24 hours, significantly increased testicular IL-6 (both protein and mRNA expression). The levels of testicular IL-6 (protein) in the homogenates were not significantly increased after stimulation with 100 microg/mL over 24 hours, but they were significantly increased at the mRNA level. Our results demonstrate, for the first time, the over-expression of IL-6 in testicular homogenates of mature and immature mice following systemic inflammation (i.p. injection of LPS). These results suggest the possibility of the involvement of systemic infection/inflammation, through the elevation of testicular IL-6, in testicular functions, which may affect male fertility. Also, high levels of IL-6 during pathological conditions, could play a role in protecting testicular tissue.

Animals↗

PubMed2005

Increasing amniotic fluid magnesium concentrations with stable maternal serum levels: a prospective clinical trial.

OBJECTIVE: To compare the effect of prolonged maternal intravenous MgSO4 administration on amniotic fluid and serum concentrations of magnesium over time in preterm labor patients. STUDY DESIGN: Patients at 24-34 weeks of singleton gestation who presented with contractions (> 8 in 60 minutes) underwent amniocentesis to rule out intrauterine infection after signing an informed consent form. Some of these women who were clinically judged to have preterm labor received intravenous MgSO4: a 4-g loading dose followed by a 2 g/h maintenance dose. For technical reasons some patients had amniocentesis performed before initiation of MgSO4 (controls), while others had the procedure during tocolytic therapy (study subjects). Duration of treatment until amniocentesis was recorded, and blood samples were drawn at the time of amniocentesis. Maternal serum and amniotic fluid magnesium levels were measured using a colorimetric end point method. Data were evaluated using the Student t test and linear regression analysis. RESULTS: Mean magnesium levels in maternal serum rose from 1.74 +/- 0.2 mg/dL in controls to 4.01 +/- 0.4 mg/dL in the study group. Mean magnesium levels in Mean magnesium levels in amniotic fluid were 1.41 +/- 0.18 mg/dL in the controls versus 2.28 +/- 0.53 mg/dL in the treatment group. Duration of MgSO4 treatment ranged from 3 to 22 hours. Amniotic fluid magnesium concentrations increased significantly during therapy (correlation coefficient = 0.89; p < 0.001), while maternal serum levels remained stable over time (correlation coefficient between maternal serum levels and time = -0.39; p=0.34). CONCLUSION: Although maternal serum magnesium levels remained stable with intravenous MgSO4 therapy, concentrations continued to rise in amniotic fluid over time. However, amniotic fluid magnesium levels never exceeded maternal serum concentrations during the study period.

Adult↗

PubMed2004

Activation of simian virus 40 promoter by HTLV-I Tax protein: role of NF-kappaB and CBP.

HTLV-I is implicated with adult T-cell leukemia and certain other clinical disorders. The viral Tax protein is regarded as a key element in HTLV-I pathogenicity due to its ability to activate a wide variety of cellular regulatory factors. As such, Tax may likely activate also latent infection of certain other pathogenic viruses whose expression is modulated by cellular transcription factors. Therefore, investigation of Tax effect on the expression of these viruses is of particular clinical importance, since HTLV-I infection of carriers harboring such latent viruses may trigger their related diseases. In this study we focused on simian virus 40 and demonstrated that Tax activates the promoter of this virus through NF-kappaB-associated pathway. Furthermore, we show that this activation requires an interaction of the NF-kappaB factor p65(RelA) with CBP, which depends on PKA-mediated phosphorylation of p65(RelA). Finally, the present study proves that the nuclear Tax plays a critical role in Tax-induced NF-kappaB-mediated SV40 activation.

CREB-Binding Protein↗

PubMed2004

Intrauterine infection/inflammation during pregnancy and offspring brain damages: possible mechanisms involved.

Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS) may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

Angiogenesis Inducing Agents↗

PubMed2004

Studies on acute human infections using FTIR microspectroscopy and cluster analysis.

A novel methodology for the diagnosis of acute infections using FTIR microspectroscopy (FTIR-MSP) data on blood components and cluster analysis is presented. Blood samples were collected from 11 patients suffering from various infections and 16 age-matched healthy human controls. Blood components such as white blood cells, red blood cells, and plasma were isolated using standard procedures and FTIR-MSP of these components was utilized. A cluster analysis of the FTIR spectra was performed. The spectra obtained from the three blood components of patients were different from those of controls. The FTIR spectra of white blood cells from patients suffering infections were significantly different from the controls. Cluster analyses of averaged FTIR-MSP spectra of white blood cells provided 100% classification between patients and healthy controls.

Acute Disease↗