A new classification system of trifid mandibular canal derived from Malaysian population.

BACKGROUND: The purpose of this study was to identify and classify the anatomic variation of mandibular canal among Malaysians of three ethnicities. MATERIALS AND METHODS: The courses of the mandibular canal in 202 cone-beam computed tomography scanned images of healthy Malaysians were evaluated, and trifid mandibular canal (TMC) when present, were recorded and studied in detail by categorizing them to a new classification (comprising of 12 types). The diameter and length of canals were also measured, and their shape determined. RESULTS: Trifid mandibular canals were observed in 12 (5.9%) subjects or 16 (4.0%) hemi-mandibles. There were 10 obvious categories out the 12 types of TMCs listed. All TMCs (except one) were observed in patients older than 30 years. The prevalence according to ethnicity was 6 in Malays, 5 in Chinese and 1 in Indian. Four (33.3%) patients had bilateral TMCs, which was not seen in the Indian subject. More than half (56.3%) of the accessory canals were located above the main mandibular canal. Their mean diameter was 1.32 mm and 1.26 mm for the first and second accessory canal, and the corresponding lengths were 20.42 mm and 21.60 mm, respectively. Most (62.5%) canals had irregularly shaped lumen; there were more irregularly shaped canals in the second accessory canal than the first branch. None of the second accessory canal was oval (in shape). CONCLUSIONS: This new classification can be applied for the variations in the branching pattern, length and shape of TMCs for better clinical description.

Potential diagnostics and therapeutic approaches in COVID-19.

The most important aspect of controlling COVID-19 is its timely diagnosis. Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. This review highlights the underlying mechanisms, advancements, and clinical limitations for each of the diagnostic techniques authorized by the Food and Drug Administration (USA). Significance of diagnosis triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted to make medical and research community more informed so that better clinical strategies are developed. We have discussed here the clinical manifestations and hospital outcomes along with the underlying mechanisms for several drugs administered to COVID-19 prophylaxis. In addition to favourable clinical outcomes, the challenges, and the future directions of management of COVOD-19 are highlighted. Having a comprehensive knowledge of the diagnostic approaches of SARS-CoV-2, and its pathogenesis will be of great value in designing a long-term strategy to tackle COVID-19.

Pioneering investigation of the characteristics and elemental concentrations in the environment of the declining Wadi Maryut Lake.

Wadi Maryut Lake is one of the remaining parts of the ancient Lake Mareotis and is not mentioned in the scientific literature. For the first time, physical and chemical characteristics as well as elemental concentrations in sediment, water, soil, and plants were determined. The lowest metal pollution indices are in the northeastern end of the lake and tend to increase toward the other end. In lake aquatic environment, Al, Fe, K, Mn, Na, B, and Cr are more likely to exist in insoluble form in the southwestern part and in soluble form in the northeastern part. Using different approaches to assess sediment contamination demonstrates that sediments can be categorized as unpolluted. However, the geo-accumulation index suggests that two locations have low anthropogenic influence of Pb and the enrichment factors and the degree of contamination indicate that Co and Pb may be enriched in sediment of some locations. Comparisons with consensus-based sediment quality guidelines revealed that no sample exceeded the probable effect concentration for Cr, Cu, Ni, Pb, and Zn. The most mobile elements in sediment-water and soil-plant systems are Na, K, and Pb. In sediment-water system, Al, Fe, and Mn oxides have the major influence on scavenging of B, K, and Cr. Similarity in the occurrences of Mn, K, and Fe in soil and Mn and Fe in wild plant was found. This work demonstrates the state of decontamination of the lake and confirms its importance as a reference and comparative case for south Mediterranean coastal water bodies.

Distribution of Molar Incisor Hypomineralization in Malaysian Children Attending University Dental Clinic.

OBJECTIVES: Molar-Incisor Hypomineralization (MIH) is a condition of hypomineralized enamel of systemic origin affecting first permanent molars and frequently permanent incisors. It is considered a global problem and data from South-East Asian countries, including Malaysia are lacking. Hence the aim of this study were to investigate the distribution and severity of MIH in a group of children aged 7-12 year olds attending pediatric dental clinic at Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Malaysia. STUDY DESIGN: Hundred and fifty four children age 7-12 year-old with mean age of 9.14 ±1.682 had their first permanent molars and permanent incisors were examined at Faculty of Dentistry, UiTM using European Academy of Paediatric Dentistry 2003 (EAPD) criteria for diagnosis of MIH. Children at least one first permanent molar affected were considered as having MIH. Data were recorded and statistically analysed using descriptive analysis and Chi square test. RESULTS: Twenty six of the total examined children (n=154) had MIH (16.9%). There was no statistical difference between males and females in the prevalence of MIH. However, a statistical significant difference was found by age groups. The first permanent molars were more frequently affected (58%) as compared to permanent incisors. Mandibular molars were to have the highest rate of MIH (15.5%). The right and left sides were equally affected. Mild defects were the most frequent lesion type (96.6%). CONCLUSIONS: This study revealed that MIH is a common condition (16.9%). Molars were more frequently affected than incisors with mild defects were the most common lesion status. Further studies on this defect amongst Malaysian children are worthwhile.

Knowledge, management and perceived barriers to treatment of molar-incisor hypomineralisation in general dental practitioners and dental nurses in Malaysia.

BACKGROUND: Molar-incisor hypomineralisation (MIH) is a global dental problem, yet little is known about the knowledge of the general dental practitioners (GDPs) and dental nurses (DNs) regarding this defect in South East Asia. AIMS: To assess and compare the knowledge of the GDPs and DNs in Malaysia regarding the frequency of occurrence of MIH within their practice, its diagnosis, putative aetiological factors and management. STUDY DESIGN AND METHODS: A questionnaire was distributed to GDPs and DNs during a nationwide dental conference in Melaka, Malaysia and who were asked to answer questions about demographic variables, knowledge, attitudes and practices in the management of MIH. STATISTICS: Descriptive statistics and bivariate analysis were performed. A 5% level of statistical significance was applied for the analyses. RESULTS: A response rate of 58.2% (131/225) was obtained. Most respondents were aware of MIH and encountered it in their practice (GDPs = 82.5%, DNs = 82.4%). The condition was observed by respondents less in primary molars compared to first permanent molars. Full agreement between GDPs and DNs did not exist concerning the aetiological factors and management of MIH. Glass ionomer cements were the most popular material used in treating MIH. Most respondents (GDPs = 93%, DNs = 76.5%) indicated that they had not received sufficient information about MIH and were willing to have clinical training in the diagnosis and therapeutic modalities of MIH. CONCLUSIONS: MIH is identified and encountered by most respondents. Agreement did not exist between GDPs and DNs concerning MIH frequency of occurrence within their practice, its diagnosis, aetiological factors and management.

Salivary trace elements in relation to dental caries in a group of multi-ethnic schoolchildren in Shah Alam, Malaysia.

AIM: To assess the salivary levels of Copper (Cu), Zinc (Zn), Manganese (Mn) and Iron (Fe) obtained from children of different ethnic backgrounds in Shah Alam, Malaysia and investigate the possible relationships with caries. MATERIALS AND METHODS: One hundred and twenty primary school children were included. They were divided into caries and caries-free groups. Unstimulated whole saliva was collected from each participant using spitting method. The salivary elements were measured using an Atomic Absorption Spectrophotometer. Descriptive statistics, bivariate and Pearson's correlation analysis were performed. RESULTS: Salivary Cu and Zn levels were significantly higher in children with dental caries compared to those caries-free (p < 0.05). Moreover, these elements had a positive correlation with dental caries (Cu: r=0.698, p<0.001; Zn: r=0.181, p<0.05). No significant variations in Mn and Fe were observed between caries and caries-free group (p>0.05). Additionally, there were significant differences in salivary Zn and Fe among different age groups (p<0.05) and highly significant differences in salivary Cu, Mn and Fe among different ethnic groups (p<0.001). However, all elements exhibited no significant differences between males and females. CONCLUSION: The salivary Cu and Zn levels showed significant differences between caries and caries-free groups. The findings also revealed significant variations in the levels of salivary Cu, Mn and Fe among different ethnic groups and salivary Zn and Fe among different age groups.

Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported to be strongly expressed in HCC tissue hampering its extensive use in clinical practice. AIM: To evaluate the clinical usefulness of serum SCCA levels as a serological marker for early detection of HCC among high-risk patients compared to AFP. MATERIALS AND METHODS: The study comprised of three groups. Group A included 30 patients with CLD diagnosed based on clinical, laboratory, and ultrasonographical investigations; group B included 49 patients with HCC diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or liver biopsy; and group C, the control group, included 15 healthy subjects matched for age and sex. All groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including liver functions, viral markers, and AFP and SCCA estimation using ELISA technique. RESULTS: This study revealed a highly significant difference between patients with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133 +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently elevated in patients with HCC with normal AFP levels representing its useful role in early detection and follow-up of patients treated for HCC. The area under the curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical significance. CONCLUSIONS: SCCA could represent a useful tool as a marker for detection of HCC.

Assessing the competency of University of Malaya dental graduates: employers' and graduates' perceptions.

A survey was conducted to assess competencies of dental graduates of the Faculty of Dentistry, University of Malaya, as perceived by the graduates and their employers, based on the five-year undergraduate curriculum introduced in 1995. All senior dental officers in the Ministry of Health (MOH), representing employers, and all 164 dental graduates of the years 2000, 2001, and 2002 were sent a self-administered questionnaire covering eight areas of competency. The respondents had to rate these areas on a scale of 1 (very poor) to 4 (very good). The responses for each area were then dichotomized into poor (1 and 2) and good (3 and 4). If less than 60 percent of the respondents rated an area as good, then it was categorized as needing attention; 60-69 percent as satisfactory; and 70 percent and above as excellent. One hundred and six graduates (64.6 percent) and twenty-nine employers (96.7 percent) responded; of the graduates, 73.6 percent were working in the MOH and 22.6 percent in private practice. About 57.1 percent of employers reported that at least five graduates have worked under them. Graduates (85.7 percent) and employers (83.3 percent) agreed that graduates have excellent skills in communication. Although all graduates perceived their competency to be excellent in the four areas (treatment planning; community-based skills; management, administrative skills, and personal management; and professional development skills), employers felt that these are the areas that are of concern and needed attention. In conclusion, whilst generally the graduates' level of competency in almost all areas is acceptable or good, there are areas of concern that need to be addressed to further improve the five-year curriculum at the University of Malaya.

Evaluation of load at fracture of Procera AllCeram copings using different luting cements.

PURPOSE: The current study investigated the effect of different luting agents on the fracture resistance of Procera AllCeram copings. METHODS: Six master dies were duplicated from the prepared maxillary first premolar tooth using nonprecious metal alloy (Wiron 99). Thirty copings (Procera AllCeram) of 0.6-mm thickness were manufactured. Three types of luting media were used: zinc phosphate cement (Elite), glass ionomer cement (Fuji I), and dual-cured composite resin cement (Panavia F). Ten copings were cemented with each type. Two master dies were used for each group, and each of them was used to lute five copings. All groups were cemented according to manufacturer's instructions and received a static load of 5 kg during cementation. After 24 hours of distilled water storage at 37 degrees C, the copings were vertically compressed using a universal testing machine at a crosshead speed of 1 mm/min. RESULTS: ANOVA revealed significant differences in the load at fracture among the three groups (p < 0.001). The fracture strength results showed that the mean fracture strength of zinc phosphate cement (Elite), glass ionomer cement (Fuji I), and resin luting cement (Panavia F) were 1091.9 N, 784.8 N, and 1953.5 N, respectively. CONCLUSION: Different luting agents have an influence on the fracture resistance of Procera AllCeram copings.

Some flexural properties of a nylon denture base polymer.

Nylon denture base material could be a useful alternative to poly (methyl methacrylate) (PMMA) in special circumstances such as patient allergy to the monomer. The aim of this study was to evaluate the flexural properties of a nylon denture base material (Lucitone FRS), a conventional compression-moulded heat-polymerized (Meliodent), a compression-moulded microwave-polymerized (Acron MC) and an injection-moulded microwave-polymerized (Lucitone 199) PMMA polymers. The effect of aldehyde-free, oxygen releasing disinfectant solution (Perform) on these properties was also investigated. The flexural modulus and the flexural strength were assessed with a three-point bending test. Specimens were stored in water at a temperature of 37 degrees C for 30 days. For each material, half of the prepared specimens were randomly selected and immersed in the disinfectant 24 h prior to testing. Results were compared statistically at a confidence level of 95%. The result showed that in both the control and disinfected groups, the flexural modulus of nylon was significantly lower than the three PMMA polymers. The flexural strength of nylon was significantly lower than those of Meliodent and Acron MC but was comparable with Lucitone 199. A 24-h immersion in the disinfecting solution increased the rigidity of nylon denture base material.

Effect of lamotrigine on the pharmacokinetics of carbamazepine and its active metabolite in dogs.

The effect of lamotrigine (LTG) on the pharmacokinetics of carbamazepine (CBZ) and its active metabolite; carbamazepine-epoxine (CBZ-E), was investigated in dogs. Five male dogs received CBZ (2 x 200 mg tab, p.o.) daily for a period of 1 week. After the end of this period, blood samples were collected serially for up to 24 hrs. After a wash-out period of I week, LTG (100 mg tab, p.o.) was coadministered with the CBZ dose (2 x 200 mg tab, p.o.) for 7 days. Blood samples were again serially collected and plasma levels of CBZ and CBZ-E were analysed by high performance liquid chromatography (HPLC). Concurrent administration of LTG with CBZ did not have any significant effect on the pharmacokinetic parameters of CBZ. There was also no significant difference between the plasma concentration ratio (CBZ-E to CBZ) vs time profiles in the two schedules of drug administration signifying the absence of pharmacokinetic interaction between LTG and CBZ or its active metabolite in this animal model.

Effect of midgut bacteria of Culex pipiens L. on digestion and reproduction.

An investigation was carried out to evaluate the influence of symbiotic bacteria associated with Culex pipiens L. on pre-oviposition and blood meal digestion periods, and reproductive potential (fecundity and fertility). Aposymbiotic females were obtained by feeding the normal females on 10% sucrose solution mixed with antibiotic (Tarivid) for three days before feeding them on normal blood meals from a pigeon host. A total of 4 genera were previously isolated from the midgut of C. pipiens. These genera were: Bacillus, Streptococcus, Staphylococcus, and Salmonella and Shigella. It seems that the period of blood meal digestion preceded the pre-oviposition period of both bacterial free females and bacterial-free females treated with one of the aforementioned bacteria. In addition, it is obviously clear that, the presence of the two bacterial genera: Bacillus and Staphylococcus in the midgut of C. pipiens is essential for normal and high fecundity. Generally, it is evident that the symbionts (gut bacteria) are essential for the completion of embryonic development.

Effect of vigabatrin and gabapentin on phenytoin pharmacokinetics in the dog.

This study was aimed at investigating whether or not the kinetics of intravenously administered phenytoin (PT) was altered by oral administration of vigabatrin (VGB) or gabapentin (GBP). A daily dose of PT (12 mgkg(-1)i.v.) was given to a group of five beagle dogs for a period of 1 week. On day eight, plasma samples were serially collected over 24 h, after administration of the PT dose. PT administration was continued, along with supplementary oral VGB (60 mgkg(-1)) for another week and then plasma samples were collected for analysis of PT levels. The same protocol was followed for the PT (12 mgkg(-1), i.v.)-GBP (300 mg caps., p.o.) study on a separate group (n= 5) of dogs. Orally administered GBP did not significantly alter the pharmacokinetic parameters of parenteral PT. However VGB markedly changed the drug's kinetics, as evidenced by a 31% (P= 0.015) reduction in total body clearance (CL) and an increase of over 45% in half-life (t(1/2)), (P= 0.013) and area under the plasma PT concentration-time curve (AUC), (P= 0.044). GBP does not appear to have any pharmacokinetic interaction with PT, while coadministration of VGB and PT results in a marked reduction in systemic clearance of the latter in the dog.

Stress distribution associated with loaded ceramic onlay restorations with different designs of marginal preparation. An FEA study.

The design of marginal finish of an inlay or onlay could influence the prognosis of the restoration since this area is subjected to various mechanical or chemical actions during function. This study was carried out to determine the tensile stresses which develop at the marginal area when subjected to vertical and horizontal loads. Onlay restorations with three different types of marginal finish, i. e. shoulder, chamfer and bevel, were modelled in three dimensions using the finite element method, and were then subjected to vertical and horizontal load at three different sites. The results show that horizontal forces acting on the restoration generate the highest tensile stresses whilst the vertical forces generate high tensile stresses at the margins of the chamfer and bevel designs.

Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog.

The study was aimed at investigating whether or not the kinetics of intravenously administered phenytoin (PT) was altered by oral administration of vigabatrin (VGB) or gabapentin (GBP). A group of five beagle dogs were given a daily dose of PT (12 mg/kg, i.v.) for a period of 1 week. On day 8, plasma samples were serially collected over 24 hr. after administration of the PT dose. PT administration was continued with oral supplementary dose of VGB (60 mg/kg) for another week and then plasma samples were collected for analysis of PT levels. The same protocol was followed for the PT (12 mg/kg, i.v.)-GBP (300 mg caps., p.o.) study on a separate group (n = 5) of dogs. Orally administered GBP did not significantly alter the pharmacokinetic parameters of parental PT. VGB, however markedly changed the drug's kinetics as evidenced by a 31% (P = 0.015) reduction in total body clearance (CL) and increase of over 45% in half-life (t1/2), (P = 0.013) and area under the plasma PT concentration-time curve (AUC), (P = 0.044). GBP does not appear to have any pharmacokinetic interaction with PT, while coadministration of VGB and PT results in marked reduction in systemic clearance of the latter in the dog.

Liquid chromatographic determination of six antiepileptic drugs and two metabolites in microsamples of human plasma.

A simple, rapid, sensitive, and reproducible high-performance liquid chromatographic (HPLC) method for simultaneous determination of the antiepileptic drugs (ethosuximide, primidone, lamotrigine, phenobarbital, phenytoin, and carbamazepine) and two metabolites (carbamazepine-diol and carbamazepine-epoxide) in human plasma is described. The procedure involves extraction of the drugs from human plasma (100 microL) with ether using 9-hydroxymethyl-10-carbamyl acridan as an internal standard. The extract was evaporated and reconstituted with mobile phase and then injected onto the chromatograph. The drugs and the internal standard were eluted from a Supelcosil LC-18 stainless steel column at ambient temperature with a mobile phase consisting of a 0.01M phosphate buffer/methanol/acetonitrile (65/18/17, v/v/v) adjusted to a pH of 7.5 with phosphoric acid and a flow rate of 1 mL/min. The effluent was monitored at 220 nm. Quantitation was achieved by using peak area ratio of each drug to the internal standard. The intraassay and interassay coefficients of variation (CV) ranged from 2.43% to 6.25% and from 3.02% to 5.85%, respectively. The absolute (extraction) and relative (analytical) recoveries for the drugs ranged from 70.7% to 104.4% and from 88.3% to 106.1%, respectively. Stability tests showed that the drugs were stable in plasma for at least 4 weeks when stored at -20 degrees C. The method was applied clinically for monitoring the AEDs in epileptic patients.

Effects of pregnancy on the pharmacokinetics of lamotrigine in dogs.

PURPOSE: This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG). METHODS: Five pregnant dogs were given a daily dose of LTG (100 mg) for a period of 1 week. Two months after parturition, the same subjects were given the LTG dose (100 mg) over the same period. On both occasions, plasma LTG concentrations were determined by a sensitive, high-performance liquid chromatographic (HPLC) method, over a 30-h period after the last dose. RESULTS: The mean maximum plasma concentration (Cmax), volume of distribution (Vd/F), and oral body clearance (Cl/F) for LTG (+/- SD) during pregnancy were 7.63+/-2.46 microg/ml 1.74+/-0.29 L/kg, and 0.19+/-0.04 L/h/kg, respectively. After pregnancy, the same variables were 6.12+/-2.24 microg/ml, 2.36+/-1.10 L/kg, and 0.30+/-0.13 L/h/kg, respectively. None of these pharmacokinetic parameters was found to be significantly different between the two groups. CONCLUSIONS: The apparent lack of change in the relevant pharmacokinetic parameters of LTG during pregnancy may indicate that pregnancy has little or no effect on glucuronidation; the principal pathway for the drug's elimination.

Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat.

The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.

Ovarian cancer-induced immunosuppression: relationship to tumor necrosis factor-alpha (TNF-alpha) release from ovarian tissue.

Cytokines have been reported to be potential biological markers of, disease status in cancer patients. Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine released from monocytes and macrophages. TNF-alpha is involved in essential biological functions such as immunoregulation, modulation of cell growth and differentiation. In this work, the role of TNF-alpha release in ovarian cancer patients was investigated. Fifty-five patients with ovarian cancer and 20 controls of matched age and parity were included in this study. TNF-alpha concentrations were measured in sera and cytosolic fractions of both groups. The results demonstrated a significant increase in TNF-alpha concentrations among patients compared to the control subjects (P < 0.001). Furthermore, a non-significant increase (P = 0.05, was observed between the different types (serous, Mucinous, and endometrioid) of epithelial ovarian cancers. Also TNF-alpha concentrations did not correlate with the disease stage. Moreover, immunohistochemical analysis of tissue specimens stained for TNF-alpha was positive in malignant lesions and negative for the normal ovarian tissue. These findings confirmed the TNF-alpha kinetics obtained by ELISA assays. Interestingly, TNF-alpha levels were also elevated in culture supernatants of PBMC stimulated by cytosolic fractions from malignant ovarian tissues. Blastogenic assays using cytosolic fractions from malignant ovarian specimens to stimulate healthy donor peripheral blood mononuclear cells (PBMC) showed a marked decrease in 3H-thymidine uptake compared to the cells stimulated by normal cytosols. To establish a cause-effect relationship between TNF-alpha release and inhibition of cell proliferation, the experiments showed that 3H-thymidine uptake by PBMC was markedly inhibited by recombinant human TNF-alpha (rh TNF-alpha) and that inhibition was significantly reversed when TNF-alpha monoclonal antibody was added to the cells. The data presented in this work indicate that TNF-alpha may play an important role in the biology of ovarian cancer and hence, tumor pathogenesis.

Cis-platinum-induced immunosuppression: relationship to melatonin in human peripheral blood mononuclear cells.

OBJECTIVES: The purpose of this study was to investigate the immunomodulatory effect of melatonin (MLT) on human peripheral blood mononuclear cells (PBMC) and to address its effects on Cis-platinum (CDDP)-induced cytotoxicity. METHODS AND RESULTS: The obtained data from this study revealed that treatment of cells with MLT (100 microg/ml) for 24 h enhanced cell viability. When cells were exposed to CDDP (5 microg/ml), cell proliferation in response to phytohaemagglutinin (PHA) stimulation was reduced by 49.63% compared to control cells as detected by 3[H]-thymidine uptake. Furthermore, Cis-platinum significantly depleted intracellular glutathione (GSH) levels by approximately 47% below that of untreated cells and led to apoptotic changes in the target cells as evidenced by DNA fragmentation (45% compared to 5% in control cells as measured by diphenylamine assay). DNA fragmentation was also confirmed by agarose gel electrophoresis. However, MLT enhanced cell proliferation by approximately 8.63% above the control values, and counteracted the antiproliferative effect of CDDP. The GSH levels were significantly increased in response to MLT (71% above control values) and it protected the cells against GSH depletion induced by CDDP. Moreover, DNA fragmentation and laddering produced by CDDP were significantly reduced or even disappeared when the cells were pretreated with MLT or the latter was simultaneously added with CDDP. CONCLUSIONS: The findings from this study indicated that melatonin is a potent immunomodulatory hormone that protects PBMC against cis-platinum-induced immunosuppressive effects. These effects might improve the patients' response to cis-platinum therapy and, therefore, their survival rates.