Saidi Moin

Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract.

The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.

Antinociceptive activity of the essential oil of Zingiber zerumbet.

In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects:

Introduction. The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in various populations in relation to hypertension (HTN) and type 2 diabetes mellitus (T2DM) with contradictory results.This study sought to determine the association of insertion (I)/D polymorphism of the ACE gene in hypertensive andT2DM subjects in a Malaysian population. Materials and methods. A total of 260 subjects consisting of 65 HTN, 60 T2DM, 65 T2DM with HTN and 70 controls were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of DD genotypes was performed with an insertion-specific primer. Results. The frequency for II, ID and DD genotypes of the ACE gene was 36.92%, 52.31% and 10.77% in HTN, 40.00%, 41.67% and 18.33% inT2DM, 30.77%, 53.85% and 15.38% inT2DM with HTN and 57.14%, 40.00% and 2.86% in controls, respectively. The frequency for the D allele was 36.92% in HTN, 39.17% in T2DM and 42.31% in T2DM with HTN compared to 22.86% in controls.The genotype and allele frequency of the ACE gene polymorphism differed significantly in patients when compared to controls (p < 0.05). Conclusion. The D allele of the ACE gene is associated with essential HTN and T2DM in Malaysian subjects.

Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells

ObjectivesWe evaluated several flavonoid combinations for synergy in the inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular model of inflammation.MethodsThe inhibitory effect of chrysin, kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric oxide (NO), prostaglandin E2 (PGE2) and tumour necrosis factor-α (TNF-α) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC50 values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC50 ratios and reassessed for inhibition of NO, PGE2 and TNF-α. Dose–response curves were generated and interactions were analysed using isobolographic analysis.ResultsThe experiments showed that only chrysin, kaempferol, morin, and silibinin were potent enough to produce dose–response effects upon at least two out of the three mediators assayed. Combinations of these four flavonoids showed that several combinations afforded highly significant synergistic effects.ConclusionsSome flavonoids are synergistic in their anti-inflammatory effects when combined. In particular chrysin and kaempferol significantly synergised in their inhibitory effect upon NO, PGE2 and TNF-α secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.

Association Between Telomere Shortening and Ageing During Occupational Exposure

Association Between Telomere Shortening and Ageing During Occupational Exposure Telomere length is considered as a biomarker of ageing, resulting in shortening during the process. The present investigation was an attempt to determine the relative telomere length in mechanical workshop workers. Telomere length shortening in cells during occupational exposure causes accelerated ageing. Genomic DNA was isolated from buccal epithelial cells collected from 240 individuals, comprising two groups of 120 exposed workers and 120 unexposed controls. Telomere length was measured by using real time PCR. Both telomere (T) and single copy gene (S) specific primers were used to compute the relative T/S ratio and expressed as the relative telomere length. Telomere length differed significantly between the workers and controls (p<0.05). The results showed an indirect and significant association (r=-0.356, p=0.001) between age and telomere length in the workers. This study showed that the difference in telomere length shortening was statistically significant (p<0.05) between the workers and controls. It was concluded that occupational exposure acts as a risk factor to enhance telomere length shortening and accelerate ageing. Veza Između Skraćenja Telomera i Starenja Usled Profesionalne IzložEnosti Dužina telomera smatra se biomarkerom starenja i tokom ovog procesa rezultira skraćenjem. Ovo istraživanje predstavlja pokušaj određivanja relativne dužine telomera kod radnika u mehaničarskim radionicama. Skraćenje dužine telomera u ćelijama tokom profesionalne izloženosti izaziva ubrzano starenje. Genomska DNK izolovana je iz epitelnih ćelija unutrašnje strane obraza sakupljenih od 240 osoba, koji su činili dve grupe: 120 profesionalno izloženih radnika i 120 neizloženih kontrolnih subjekata. Dužina telomera izmerena je tehnikom PCR u realnom vremenu. Specifični prajmeri telomera (T) i gena prisutnih u jednoj kopiji (S) upotrebljeni su za izračunavanje relativne razmere T/S i izraženi kao relativna dužina telomera. Dužina telomera značajno se razlikovala između radnika i kontrolnih subjekata (p<0,05). Rezultati su pokazali da između starosti i dužine telomera kod radnika postoji indirektna i značajna povezanost (r=-0,356, p=0,001). Ova studija je pokazala da je razlika u skraćenju dužine telomera između radnika i kontrolnih subjekata bila statistički značajna (p<0,05). Zaključeno je da profesionalna izloženost predstavlja faktor rizika za znatnije skraćenje dužine telomera i ubrzano starenje.

Does GSTP1 polymorphism contribute to genetic damage caused by ageing and occupational exposure

Does GSTP1 Polymorphism Contribute to Genetic Damage Caused by Ageing and Occupational Exposure? The aim of our study was to see the effects of GSTP1 polymorphism on biomarkers of ageing, including micronuclei (MN), comet tail length, and relative telomere length in automobile repair workers, who are exposed to a broad spectrum of potential mutagens. The analysis was performed on buccal cells collected from occupationally exposed and non-exposed (control) subjects. Samples were analysed using cytogenetic and molecular methods, including restriction fragment length polymorphism (RFLP), MN test, comet assay, and real-time PCR. The results confirmed the DNA damaging effects of substances used in the mechanical workshops, but did not confirm the influence of GSTP1 gene polymorphism on DNA damage. However, further studies on both occupationally exposed and control populations are needed to understand the relationship between GSTP1 polymorphism and genome damage. Pridonosi li polimorfizam gena GSTP1 oštećenju genoma uzrokovanom starenjem i profesionalnom izloženosti? Na populaciji radnika zaposlenih u radionicama za popravak automobila koji su svakodnevno izloženi različitim vrstama potencijalnih mutagena istražili smo utjecaj polimorfizma gena GSTP1 na vrijednosti biomarkera starenja, uključujući pojavu mikronukleusa (MN), dužinu repa kometa te relativnu dužinu telomera. Analize su provedene na stanicama bukalne sluznice, skupljenim od izloženih ispitanika i odgovarajuće neizložene (kontrolne) populacije. Uzorci su analizirani primjenom citogenetičkih i molekularnobioloških metoda, uključujući polimorfizam restrikcijskih fragmenata na osnovi njihove duljine (engl. restriction fragment length polymorphism, RFLP), MN-test, komet-test, i lančanu reakciju polimerazom u stvarnom vremenu (engl. real-time PCR). Dobiveni nalazi potvrđuju da izloženost radnika mutagenima oštećuje njihovu DNA, ali nisu pokazali da polimorfizam gena GSTP1 značajno utječe na razinu oštećenja DNA. Zbog malog broja ispitanika uključenog u ovo istraživanje za bolje razumijevanje odnosa između polimorfizma gena GSTP1 i oštećenja DNA potrebna su daljnja istraživanja, i na profesionalno izloženim ispitanicima i na ispitanicima kontrolne populacije.

Antinociceptive and antiinflammatory activities of the aqueous extract of Trigonopleura malayana resin in experimental animal models.

Trigonopleura malayana L. (Euphorbiaceae) resin, locally known as Gambir Sarawak, has been used traditionally to alleviate pain associated with insect bites, muscle ache, toothache and minor injuries. The present study was carried out using various animal models to determine the antinociceptive and antiinflammatory activities of the T. malayana resin aqueous extract. Antinociceptive activity was measured using the abdominal constriction, hot plate and formalin tests, while antiinflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 24 h of soaking the dried resin in distilled water, was prepared in doses of 0.3, 3 and 10 mg/kg and administered subcutaneously 30 min prior to the assays. The mechanism of action was also determined by prechallenging with naloxone (10 mg/kg), a nonselective opioid antagonist. The extract was found to exhibit significant (P < 0.05) and dose-dependent antinociceptive and antiinflammatory activities; naloxone failed to inhibit the former activity. In conclusion, the aqueous extract of T. malayana resin possesses nonopioid antinociceptive and antiinflammatory activities, thus supporting previous claims regarding its traditional use by the Malays to treat various ailments, particularly those related to pain.

Role of the CYP1A2 Gene Polymorphism on Early Ageing from Occupational Exposure.

ABSTRACT The ageing process is influenced by many internal and external factors. The toxic substances in the environment can cause genomic damages to cells, which increase the risk of early ageing. Furthermore, the cytochrome P450 1A2 (CYP1A2) gene polymorphism is a susceptibility factor and may enhance the risk of DNA damage in cells. The current study was carried out to show whether occupational exposure could cause genotoxicity in cells carrying the CYP1A2 gene polymorphism, thus enhancing the likelihood of early ageing. This study was conducted on mechanical workshop workers and a control group by collecting buccal cells from their mouths. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to identify the CYP1A2 gene polymorphism in the cells. In addition, three extra methods including micronuclei (MN) test, comet assay and real-time PCR (RT-PCR) were applied to determine the effects of gene polymorphisms on DNA damage and ageing from occupational exposure. The results showed that DNA damage in the cells carrying the mutated genotype was higher than the wild genotype. In addition, the difference in MN frequency (p = 0.001) and relative telomere length (p = 0.002) between workers and controls was significant (p <0.05) in the mutated genotype. The findings indicated a possible protective effect of gene polymorphism against early ageing, which was characterized by lack of a significant influence of CYP1A2 gene polymorphism on genetic material in the subjects (p >0.05). It was concluded that the CYP1A2 gene could be a contributing factor to prevent early ageing from occupational exposure.

Amplification of real-time high resolution melting analysis PCR method for polycystic kidney disease (PKD) gene mutations in autosomal dominant polycystic kidney disease patients

PKD1 and PKD2 are the two genes responsible for the development of autosomal dominant polycystic kidney disease (ADPKD). PKD1 gene mutations accounts for ≈85% of all ADPKD cases, while the remaining ≈15% of cases is caused by mutations in the PKD2 gene. Genotyping for PKD1 and PKD2 mutations was usually identified using conventional polymerase chain reaction (PCR) or PCR-single stranded conformation polymorphisms (SSCP) methods. In this study, we assessed the usefulness of eight common primers amplifying the respective genes in real-time high resolution melting analysis PCR (real-time HRMA PCR) in terms of time, cost and sensitivity with respect to PCR-SSCP method. We found that case sample can easily be differentiated from control sample by melting curve profile difference, although a primer was found to be less useful. We concluded that real-time HRMA PCR is a rapid and sensitive method to categorize samples based on the melting curve profiles with comparable sensitivity to conventional PCR-SSCP.