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Introduction Nitric oxide (NO) is produced in different cell types through the action of specific neuronal and nonneuronal nitric oxide synthases on L-arginine as a substrate. NO plays a major [...], Since both morphine and tadalafil have been proven to exert some of their analgesic activity through modulation of the NO-cGMP pathway, the aim of the current study is to evaluate the pharmacologic interaction between tadalafil and morphine to decrease the dose of morphine and subsequently its side effects. The assessment was carried out through isobolographic analysis relative to [ED.sub.50]s of both morphine and tadalafil obtained by tail-flick test on BALB/c mice. Morphine and tadalafil [ED.sub.50]s calculated from the dose-response curves were 8303 and 2080 [micro]g/kg, respectively. The experimental [ED.sub.50] values of morphine and tadalafil in their mixture were 4800 and 1210 [micro]g/kg, respectively. Those results showed an additive interaction between morphine and tadalafil presented by a total fraction value for the mixture of 1160 [micro]g/kg. This outcome can be interpreted by the fact that both drugs share common pathways, namely, NO-cGMP and opioid receptors. As a conclusion, the morphine and tadalafil combination showed an additive effect against acute pain, which is mediated through the central nervous system, thus providing a rationale for combining them to decrease morphine dose and thus minimizing its side effects. Key words: antinociception, analgesia, drug interaction, isobolographic analysis, morphine, nitric oxide, phosphodiesterase 5 inhibitor, tadalafil. Puisqu'on a montre que la morphine et le tadalafil exercent tous deux une partie de leur activite analgesique par l'intermediaire de la modulation de la voie de signalization NO-GMPc, le but de la presente etude etait d'evaluer l'interaction pharmacologique entre le tadalafil et la morphine afin de diminuer la dose de morphine et par le fait meme ses effets indesirables. L'evaluation a ete menee par l'etude isobolographique par rapport a la [DE.sub.50] de la morphine comme du tadalafil obtenue a l'aide du test de retraction de la queue chez des souris BALB/c. Les [DE.sub.50] de la morphine et du tadalafil calculees a partir des courbes doses-reponse etaient de 8303 et de 2080 [micro]g/kg, respectivement. Les valeurs experimentales de [DE.sub.50] de la morphine et du tadalafil dans leur melange etaient de 4800 et de 1210 [micro]g/kg, respectivement. Ces resultats ont montre la presence d'une interaction additive entre la morphine et le tadalafil representee par une valeur fractionnelle totale de 1160 [micro]g/kg pour le melange. Ce resultat peut s'interpreter par le fait que les effets des deux medicaments passent par les memes voies de signalisation. : NO-GMPc et celle des recepteurs aux opiaces. En conclusion, l'association de la morphine avec le tadalafil a montre un effet additif contre la douleur aigue mediee par le systeme nerveux central, ce qui apporte une rationnelle pour les associer l'un avec l'autre afin de diminuer la dose de morphine et donc de diminuer au minimum ses effets indesirables. Mots-cles: antinociception, analgesie, interaction medicamenteuse, etude isobolographique, morphine, oxyde nitrique, inhibiteur de la phosphodiesterase 5, tadalafil.

Type-2 diabetes mellitus (T2DM) is a chronic disorder characterized by a varying range of predominant insulin resistance with relative insulin deficiency, to predominant insulin secretory defect with or without insulin resistance. Familial clustering as well as epidemiological studies has shown that genetic factors play a role in the development and progression of the disease. Among the genetic factors found to be associated with development of T2DM is the angiotensin-I converting enzyme (ACE) gene, which is located on chromosome 17q23. This study was conducted to study the association between ACE gene insertion/deletion (I/D) polymorphism and T2DM in a Lebanese diabetic cohort. Fifty-one patients with T2DM and 40 control subjects from different parts of Lebanon underwent genotyping for the ACE I/D, which was performed by PCR using specific primers. Chi-square and analysis of variance (ANOVA) were used for asso-ciation studies and to assess the differences in the values among the groups. The distribution of the genotypes in the patients was as follows: 15/51 (29.4%) were homozygous for deletion allele (DD genotype), 24/51 (47.1%) were heterozygous (ID genotype), and 12/51 (23.5%) were homo-zygous for insertion allele (II genotype). Among the control subjects, 16/40 (40%) were homo-zygous for deletion (DD genotype), 13/40 (32.5%) were heterozygous (ID genotype), and 11/40 (27.5%) were homozygous for insertion (II genotype). The prevalence of the D-allele in T2DM patients (52.9%) was not significantly different from that in the controls (56.3%). Thus, ACE I/D dimorphism cannot be considered a risk factor for T2DM in the Lebanese population.

CONTEXT: Asthma is a complex inflammatory condition often associated with bronchial hyper reactivity and atopy. Genetic and environmental factors are implicated in the etiopathogenesis of asthma. Regulated upon Activation Normal T- cell Expressed and Secreted (RANTES) is a CC chemokine responsible for the recruitment of inflammatory cells, suggesting a possible role for this chemokine in asthma. Both -403A and -28G alleles of the RANTES promoter region were found to be associated with asthma/atopy in some but not all studies. AIM: The purpose of this study was to investigate the genetic influence of -403A and -28G alleles of the RANTES promoter region on the development of asthma in Lebanon. SETTINGS AND DESIGN: This case control study was conducted at Makassed Hospital, Beirut on 40 asthmatic patients and 38 healthy controls. METHODS: RANTES gene polymorphisms -403G/A and -28C/G alleles were genotyped using PCR.RFLP. RESULTS: No significant differences in allele or genotype frequencies for the RANTES gene polymorphisms between asthmatic patients and controls were found. The difference of the -403 GA genotype frequency between patients and controls was not statistically significant; (OR=0.8, 95% CI=0.2-2.3, P=0.8). Similarly, the difference of the A.allele frequencies between patients and controls was not significant (OR=0.824, CI=0.3-2.2, P=0.7). CONCLUSIONS: Our data show that RANTES gene promoter polymorphisms are not associated with asthma susceptibility in the Lebanese population. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a family of enzymes that degrade extracellular matrix components and are involved in the development and progression of cancer. Lung cancer is the most commonly diagnosed cancer in Lebanon. This study was undertaken to investigate the association between -1171(5A>6A) polymorphism in the promoter of MMP3 gene and the susceptibility to lung cancer in a Lebanese population. The MMP3 polymorphism was investigated in 41 lung cancer patients and 51 unrelated healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found a significant association between MMP3-1171 5A allele and lung cancer (Odds ratio [OR]=2.7, 95% [CI]=1.3-5.3; Fisher's p-value=0.005). This study may form an additional evidence for the association of MMP3 enzyme and genetic susceptibility to lung cancer.

Type-1 diabetes mellitus (T1DM) is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting β-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1)], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12) on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP) technique and to investigate the association of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in Lebanese T1DM patients. The study was conducted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, suggesting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was observed. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

Objective: To investigate the association of the 2 intracellular adhesion molecules-1 (ICAM-1) gene polymorphisms [thymidine/cytidine (T/C) 469 and guanosine/adenosine (G/A) 241] in Behcet`s disease in Lebanon., Methods: We initiated the study in July 2003, and carried out the work in the research laboratory of Beirut Arab University, Beirut, Lebanon. We extracted the DNA by glass fiber matrix mini column. We amplified the ICAM gene by polymerase chain reaction (PCR) and tested the PCR products for the presence of the polymorphisms using a restriction enzyme specific for each polymorphism. We analyzed the results by agarose electrophoresis., Results: We demonstrated the association of only one single nucleotide polymorphism (SNP) (K469) with Behcet`s disease, while we could not detect the other SNP (G241A) in either controls or patients in the Lebanese population., Conclusion: The ICAM-1 gene polymorphism 469 T/C, but not 241 G/A, may encode risk for Behcet`s disease in the Lebanese population.

The effect of the commonly used spice extracts cinnamon and clove and their main ingredients on the activity of various ATPases were investigated. Water extracts of both spices inhibited the activity of rat liver Na+/K+ ATPase, and Cu2+-ATPase, but stimulated F0F1ATPase. Similar effects were obtained with cinnamaldehyde and eugenol the major components of cinnamon and clove, respectively with eugenol being more potent. The 50% inhibition of the P-type Na+/K+ ATPase was obtained at 4.7 +/- 0.04 mM for cinnamaldehyde and 1.1 +/- 0.02 mM for eugenol. The 50% inhibition of the CPx-type Cu2+ ATPase was obtained at 0.94 mM for cinnamaldehyde and 0.65 mM for eugenol. On the other hand both compounds stimulated significantly the mitochondrial F0F1ATPase. The shared structural and functional similarities between the P- and the CPx-classes of ATPases may underlie the common effect exhibited by both but not the F-ATPase. Our results identify Na+/K+ ATPase, Cu2+-ATPase and F0F1ATPase as possible intracellular targets for the action of spices' components that result in: a decrease in ATP level, defects in proton and ion transports leading to electrolyte imbalance and derangements in mitochondrial function.