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Dihydrofolate (dihydrofolic acid, vitamin B9) is one of the principle reduced forms of folates, which is converted to tetrahydrofolate by dihydrofolate reductase (DHFR). The aim of the present stud...

Cadmium toxicity can disturb brain chemistry leading to depression, anxiety, and weakened immunity. Cadmium disturbs the neurotransmitter dopamine, resulting in low energy, lack of motivation, and depression, which are predisposing factors for violence. The purpose of this study was to evaluate the ameliorative effect of grape seed extract (GSE) on the brain of 40 male albino rats after exposure to cadmium chloride (Cd) toxicity. The rats were separated into either the control group, the Cd group, the GSE group, or the GSE and Cd mixture (treated) group. The cerebrum showed evidence of degeneration of some nerve fibers and cells. Fibrosis, vacuolations, and congestion in the blood vessels were demonstrated. Satelletosis was located in the capsular cells. Immunohistochemical expression of Bax was strongly positive in the Cd group and decreased in the treated group. These histopathological changes were decreased in the brain tissue of the treated group, but a few blood vessels still had evidence of congestion. Cadmium administration increased the level of MDA and decreased MAO-A, acetylcholinesterase, and glutathione reductase (GR), while the treatment with GSE affected the alterations in these parameters. In addition, cadmium downregulated the mRNA expression levels of GST and GPx, while GSE treatment normalized the transcript levels. The expression of both dopamine and 5-hydroxytryptamine transporter was downregulated in the rats administered cadmium and the addition of GSE normalized the expression of these aggression associated genes.

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000ft above the sea level). Iron supplementation (2mg elemental iron/kg, once daily for 15days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25mg/kg, once daily for the last 7days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures.

The prevalence of autism in Saudi Arabia is 18 per 10,000, higher than the 13 per 10,000 reported in developed countries. The etiology of autism is still not completely understood. Different studies support the involvement of dopaminergic neurotransmitter system in the etiology of autism. Several lines of evidences suggest the role of some dopamine related genes, such as DRD1 and SLC6A3 in the etiology of autism. The aim of the present work was to study the possible role of rs2550936 A/C polymorphism at SLC6A3 locus as well as rs4532 A/G polymorphism at DRD1 locus in the etiology of autism among Saudi population. The polymorphisms of DRD1 and LC6A3 were genotyped in the case-control study using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Significant association as risk factor was found between autism and GA genotype of DRD1 [OR = 3.5 CI (1.04, 12.41*)] as well as CA genotype of SLC6A3 [OR = 2.53 CI (1.03, 6.26*)], while CC genotype of SLC6A3 revealed protective effect. In conclusion, possible risk genotypes for autism in the DRD1 and SLC6A3 genes were observed. This is the first report in Saudi Arabia population and Arab world. Therefore further investigations of these markers and other SNPs of SLC6A3 and DRD1 genes are considered in large replication samples with other causal factors to enable positive identification of risk genotypes and generalize obtained results. Key words : Etiology, polymorphism, autism, genotype.

Mobile phones are increasingly used by professionals, university staffs and health care personnel for communication. These can harbor various potential pathogens. This study evaluates and identifies the bacterial contamination rate of mobile phones in the university setting that are in frequent contact with faculty members, personnel, students and/or physicians and nurses in the university clinic. A total of 101 mobile phones belonging to different categories working in various departments at Taif University, KSA were screened for microorganisms’ contamination. Out of the total 101 mobile phones, growth was obtained in 78 (77.2%) mobile phones; 70 (89.7%) from staffs, personnel, students and 8 (10.3%) from clinical workers. Staphylococcus spp and Bacillus spp were the most commonly isolated organisms. Coagulase negative Staphylococcus was the most frequently isolated; 60 (27.12%). The efficacy of decontamination with 70% isopropyl alcohol was found to be 71.3%, as only 29 mobile phones showed growth after decontamination. It was found that around 61.5% of the mobile phones of health care workers at university clinic were contaminated and thus acted as a potential source of nosocomial infections. According to morphological, physiological characteristics, APi profiles and sequencing of 16S-rRNA gene, the selected eight isolates were identified as Bacillus pumilus, Bacillus cereus, Staphylococcus aureus, Staphylococcus hominis, Staphylococcus succinus, Staphylococcus xylosus and Staphylococcus saprophyticus. Based on random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), 32 unique RAPD fragments were identified among the selected isolates. Such unique fragments could be considered as specific markers and might be utilized in tracking the bacterial isolates. Key words : Mobile phones, contamination, pathogen carriers, coagulase negative staphylococci, Bacillus species, 16S-rRNA, random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR).

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4 %. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30 bp-promoter VNTR and DAT1 40 bp 3′ UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95 % confidence interval (95 % CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P

This work was carried out in order to develop early flowering barley lines. These lines will be useful to producers by enabling multiple crops within a single season and increasing production. Transgenic barley plants containing the natural early flowering time AtCRY2 allele from the Cape Verde Island (Cvi) ecotype of Arabidopsis have been generated using biolistic transformation. Immature embryo derived calli of two commercially important barley cultivars (El-Dwaser and El-Taif), were transformed using a pCAMBIA-2300 plasmid harboring a genomic fragment containing the AtCRY2-Cvi allele. Transformation was performed utilizing 600 immature embryos for each cultivar. Stable transformation was confirmed in T 0 and T 1 plants by using genomic PCR, RT-PCR and western blot analysis with AtCRY2 specific primers and antibodies, respectively. The transformation efficiency was 5.6% and 3.4% for El-Dwaser and El-Taif cultivars, respectively. Seeds from several T 1 lines were germinated on kanamycin plates and the lines that contained a single locus were selected for further evaluation. The transformed barley plants showed the specific AtCRY2-Cvi flowering phenotype, i.e. early flowering and day length insensitivity, compared to the non transgenic plants. The time to flowering in transgenic T 1 plants was assessed and two lines exhibited flowering more than 25 days earlier than the parental cultivars under short day conditions.

Problem statement: Laboratory diagnosis of breast cancer in most of the hospitals has traditionally been performed using cell culture and the direct hormone receptor assay, which are money and time consuming. Approach: This study was performed in order to direct the attention toward increasing the efficiency of early diagnosis in clinical laboratories at the western region of KSA and Egypt using recent PCR-dependent protocols i.e., Randomly Amplified Polymorphic DNA (RAPD’s) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Expression of HER4 oncogene using RT-PCR and immunohistochemical (IHC) staining have been assessed as early diagnostic for breast cancer. RT-PCR has detected HER4 expression in 52% of Invasive Duct breast Cancer (IDC) and this expression was significantly correlated with HER4 gene expression by IHC. Also we have selected sixteen 10-mer RAPD primers that have shown high percentage of identity to exons of different human oncogenes, such as V-myc, HER2, HER4, BRCA1 and BRCA2. Results: Only 13 out of the selected RAPD primers have revealed 19 distinguishable polymorphic markers between patient and normal females. Moreover, analysis of total protein profile identified extra markers and some differences at the level of Low Molecular Weight (LMW) protein among the two classes of females. Conclusion: These data will provide molecular, biochemical and pathological markers that can be used in KSA and Egypt clinical laboratories as additional efficient tools for early diagnosis of breast cancer.

Ratio subtraction and isosbestic point methods are 2 innovating spectrophotometric methods used to determine vincamine in the presence of its acid degradation product and a mixture of cinnarizine (CN) and nicergoline (NIC). Linear correlations were obtained in the concentration range from 840 g/mL for vincamine (I), 622 g/mL for CN (II), and 636 g/mL for NIC (III), with mean accuracies 99.72 0.917 for I, 99.91 0.703 for II, and 99.58 0.847 and 99.83 1.039 for III. The ratio subtraction method was utilized for the analysis of laboratory-prepared mixtures containing different ratios of vincamine and its degradation product, and it was valid in the presence of up to 80 degradation product. CN and NIC in synthetic mixtures were analyzed by the 2 proposed methods with the total content of the mixture determined at their respective isosbestic points of 270.2 and 235.8 nm, and the content of CN was determined by the ratio subtraction method. The proposed method was validated and found to be suitable as a stability-indicating assay method for vincamine in pharmaceutical formulations. The standard addition technique was applied to validate the results and to ensure the specificity of the proposed methods.

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvet. Linear relationships were obtained in the ranges of 6–22 μg/mL for the (1D) method and 6–20 μg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 ± 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 ± 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of ≤10% (II) and ≤50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.

Three methods are presented for the determination of trimetazidine dihydrochloride in the presence of its acid-induced degradation products. The first method was based on measurement of first-derivative D1 value of trimetazidine dihydrochloride at 282 nm over a concentration range of 8.00–56.00 μg/mL with mean percentage accuracy of 99.80 ± 1.17. The second method was based on first derivative of the ratio spectra DD1 at 282 nm over the same concentration range with the percentage accuracy of 99.14 ± 0.68. The third method was based on separation of trimetazidine dihydrochloride from its acid-induced degradation products followed by densitometric measurement of the spots at 215 nm. The separation was performed on silica gel 60 F254 using methanol–ammonia (100 + 1.5, v/v) as mobile phase. This method was applicable for determination of the intact drug in the presence of its degradation products over a concentration range of 2.00–9.00 μg/spot with mean percentage accuracy of 99.86 ± 0.92. The proposed methods were successfully applied for the determination of trimetazidine dihydrochloride in bulk powder, laboratory-prepared mixtures containing different percentages of degradation products, and pharmaceutical dosage forms. The validity of results was assessed by applying the standard addition technique. The results obtained agreed statistically with those obtained by the reported method.

Iron supplementation is recommended at high altitudes to meet the demand for the high altitude-associated physiological polycythemia. Iron is a major player in redox reactions and may exacerbate th...

A sensitive stability indicating method for the determination of nizatidine in the presence of its degradation products is developed. The proposed method is based on measuring the peak heights of the first derivative spectra at 680 nm of the blue reaction product developed from the reaction of nizatidine with 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the presence of ferric chloride. The concentration of MBTH, and type of oxidising agent and its concentration were studied over time. The suggested procedure is simple, rapid and readily adaptable for the determination of pure nizatidine in bulk powder. Laboratory prepared mixtures and pharmaceutical preparations in the range of 1.6–8 μg · ml−1 of reaction mixture can be analysed. The results obtained were compared statistically with those obtained by applying the official USP XXIII (1995) method. Furthermore, the validity of the results was assessed by applying the standard addition technique.

Spectrophotometric methods were developed for the determination of glafenine and floctafenine. The first method depends upon the determination of glafenine in raw material and tablets as well as in the presence of its main degradation product glafenic acid (up to 40%). Differential first derivative spectral response at 245 nm in 0.1 N hydrochloric acid, where the corresponding degradation product exhibits no contribution in 0.1 N sodium hydroxide. The method allows the determination of 2.5-30 microg ml(-1). The second method depends upon the reaction of floctafenine with 2,3-dichloro 5,6-dicyano-p-benzoquinone (DDQ) in acetonitrile to give highly colored complex that could be measured quantitatively at (about) lambda(max) 538 nm. The method permits the determination of 40-180 microg ml(-1) or by measuring the first derivative spectral response of the color at 610 nm. The method permits the determination of floctafenine in presence of thiocolchicoside. The methods mentioned both simplicity and sensitivity, having excellent precision and accuracy (100.31 +/- 0.63, 100.78 +/- 0.77 and 99.90 +/- 0.56 for glafenine and floctafenine, respectively). The results were of comparable accuracy and reproducibility with the reported methods.

A colorimetric method for the quantitative determination of diclofenac sodium and mefenamic acid in pure form and in pharmaceutical preparations was developed. It was based on the inter-action of the secondary aromatic amine with p-dimethyl-aminocinnamaldhyde in acidified absolute methanol medium to form very stable red [λmax at 538 nm in case of diclofenac sodium] or blue [λmax at 665 nm in case of mefenamic acid] products. Beer's law was obeyed over the ranges 10–80 μg ml−1 and 1–8 μg ml−1 for diclofenac sodium and mefenamic acid, respectively. The reactants were heated on a boiling water bath for 6 and 5 mins for each drug, respectively. Optimization of the different experimental conditions were studied. The mean percentage recoveries were found to be 100.73 ± 0.87% & 100.73 ± 0.44%, respectively. The method was applied successfully for the determination of some pharmaceutical formulations. The validity of the suggested procedure was assessed by applying the standard addition technique.

FXIII gene Val34Leu variant appears to be associated with decreased risk of myocardial infarction and venous thromboembolism as well as with increased risk of intracerebral hemorrhage. Fibrinogen β-gene SNP -455G/A are associated with differences in the plasma levels of fibrinogen and severity of arterial disease. The aim of the present work was to study the prevalence of FXIII gene V34L and Fibrinogen β-gene -455G/A SNPs in Saudi population. Among 200 blood samples randomly collected from unrelated healthy Saudi subjects, FXIII gene V34L and Fibrinogen β-gene -455G/A SNPs were genotyped via cardiovascular disease (CVD) StripAssay (ViennaLab, Austria. Homozygous (V/V) and heterozygous (V/L) genotypes were detected with 96 and 4%, respectively, among FXIII gene V34L genotypes, whereas (L/L) genotype was not found. The allele frequency was 0.98 for V allele and 0.02 for L allele. Three genotypes of Fibrinogen β-gene -455G/A SNP (GG, GA and AA) were obtained and its prevalence (%) was 70, 25 and 5, respectively. The frequency of G allele was 0.825 and 0.175 for A allele. Prevalence of FXIII gene Vl34L polymorphism and its allele frequency are in line with other Asian populations. Distribution of β-gene -455G/A genotypes and allele frequency are in accordance with previous reports in different ethnic groups. This is the first time to report these polymorphisms in Saudi Arabia population. This study provides valuable information on Saudi genetic background in comparison with other populations. In addition, it serves as a template for future clinical research involving cardiovascular and cerebrovascular diseases. Key words : FXIII gene V34L, fibrinogen β-gene -455G/A, polymorphisms, Saudi Arabia.

The Present work describes a direct flow injection analysis (FIA) of five commonly used central nervous system (CNS) acting drugs namely amitriptyline hydrochloride, carbamazepine, clomipramine hydrochloride, fluphenazine hydrochloride and imipramine hydrochloride. The characteristics of the system and the conditions of the speatrophotometric determination are evaluated. The proposed technique can be applied for pharmaceutical quality control of the pure material and pharmaceutical dosage forms containing the drug. Amount ranging from 16 to 80 μg. ml−1 of amitriptyline hydrochloride. The Present work describes a direct flow injection analysis (FIA) of five commonly used central nervous system (CNS) acting drugs namely amitriptyline hydrochloride, carbamazepine, clomipramine hydrochloride, fluphenazine hydrochloride and imipramine hydrochlorode. The characteristics of the system and the conditions of the spectrophotometric determination are evaluated. The proposed technique can be applied for phar...

A simple, accurate, and reliable titrimetric method is described for the determination of six antimony(III) compounds, namely: antimony(III) oxide, antimony(III) chloride, tartar emetic, bilharcid, astiban, and anthiomaline. The suggested method involved the use of N,N -dibromodiethylbarbituric acid (5 × 10 −3 M ) solution as titrant. The detection of the end point could be accomplished either visually, using dye-stuffs as indicators, or potentiometrically using a platinum/calomel electrode system. Alternatively, spectrophotometric titration was also performed. The molar reactivity was assessed and a proposed reaction pathway is presented. The suggested method was applied to the determination of the studied compounds in dosage forms, and the results compared favorably with the official or published methods.

In this work the reaction between oxamniquine as n donor and iodine as sigma acceptor was studied,. Different parameters involved in the reaction were investigated such as choice of solvent, iodine concentration, time, light and temperature. Also the stoichiometry of the reaction was determined. Thus, a spectrophotometric procedure has been developed for the determination of oxamniquine by reaction with iodine and measurement of absorbance of the formed charge transfer complex at λ 291 and λ 360 nm. Molar absorptivities, A 1%, 1 cm and the regression equations were computed. The proposed procedure was applied for the determination of oxamniquine in its dosage forms. Accurate and precise results were obtained when compared to the manufacturer's procedure.

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for the determination of meclophenoxate hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their degradation products are described. The sensors are based on the use of the ion-association complexes of (I) and (II) cation with sodium tetraphenyl borate and ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In addition beta-cyclodextrin (beta-CD) membranes were used in the determination of I and II. These ion pairs and beta-CD were then incorporated as electroactive species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta-cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB), (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73, 51.64 and 54.05 per concentration decade with average recoveries of 99.92+/-1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta-CD respectively. Pyritinol also showed near Nernestian responses over the concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit-RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10 and 32.89 per concentration decade and average recoveries of 99.99+/-0.827, 100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD respectively. The sensors were used successfully for the determination of I and II in laboratory prepared mixtures with their degradation products, in pharmaceutical dosage forms and in plasma.

This work is concerned with the simultaneous determination of domperidone maleate (DOM) and cinnarizine (CINN) in a binary mixture form without previous separation by two different methods. The first method is the application of derivative ratio spectrophotometry where the linearity range was 2.5-30 micro g/ml, 2.5-25 micro g/ml for DOM and CINN, respectively, and percentage recoveries were 100.26+/-1.308 and 99.86+/-0.939 for DOM and CINN, respectively, in their laboratory prepared mixtures. The second method depends on the application of classical least squares (CLS) calibration model. Two training sets were constructed and the best model was used for the prediction of the concentrations of both drugs. The proposed procedures were successfully applied for the simultaneous determination of both drugs in laboratory prepared mixtures and in commercial tablet preparations. The validity of the proposed methods was assessed by applying the standard addition technique where the percentage recovery of the added standard was found to be 99.83+/-1.861 and 98.38+/-0.871 for DOM and CINN, respectively, using the derivative ratio method and 99.53+/-0.916 and 99.39+/-0.599 for DOM and CINN, respectively, using the CLS method. The proposed procedures are rapid, simple, require no preliminary separation steps and can, therefore, be used routine analysis of both drugs in quality control laboratories.

This work is concerned with the simultaneous determination of domperidone maleate (DOM) and cinnarizine (CINN) in a binary mixture form, without previous separation, by two different techniques. The first method is the application of derivative spectrophotometry where the linearity range and percentage recoveries for DOM and CINN were 2.5-30 micro g mL(-1), 5-25 micro g mL(-1) and 100.06+/-1.157, 99.93+/-1.377, respectively. The second method depends on the application of partial least squares (PLS) and principle component regression (PCR) models. A training set consisting of 10 mixtures containing 5-20 micro g mL(-1) for each component was used for the construction of the PCR and PLS models. These models were used after their validation for the prediction of the concentration of DOM and CINN in their mixtures. The proposed procedures were successfully applied for the simultaneous determination of both drugs in laboratory prepared mixtures and in commercial tablet preparations. The validity of the proposed methods was assessed by applying the standard addition technique where the percentage recovery of the added standard was found to be 99.98+/-0.297 and 99.84+/-0.700 for DOM and CINN, respectively, using the derivative spectrophotometric method and 100.29+/-0.398 and 100.11+/-0.363 for DOM and CINN, respectively, using the PLS and PCR methods. The proposed procedures are rapid, simple, require no preliminary separation steps and can be used for routine analysis of both drugs in quality control laboratories.

The clastogenic effect of the anticancer drug cis-diamminedichloroplatinum (II) (cisplatin) on meiotic prophase in primary spermatocytes and on spermatogonial stem cells of male (101/E1 x C3H/E1)F1 mice was studied. The intraperitoneal doses of cisplatin tested were 5.0, 7.5 and 10.0 mg/kg. Chromosomal aberrations were examined at diakinesis-metaphase 1 of meiosis 1-13 days after treatment, representing cells treated at diplotene, pachytene, zygotene, leptotene an preleptotene. Reciprocal translocations were evaluated 63-70 days after treatment, representing treated stem-cell spermatogonia. Cisplatin had a toxic effect in zygotene to preleptotene of meiosis, as indicated by the significant reduction in testicular weight. At diplotene, pachytene and zygotene no enhancement of aberrations was found. An increase in aberrant cells was observed during leptotene with preleptotene being the most sensitive stage. The dose-response relationship for aberrant cells was linear on day 13 after treatment. It is concluded that, like mitomycin C (Adler, 1976), cisplatin primarily caused aberrations during the premeiotic phase of DNA synthesis. No significant increase of translocation multivalents was found after treatment of stem-cell spermatogonia.

Two pH- induced difference- spectrophotometric procedures for the determination of oxyphenbutazone in pharmaceutical formulations are reported. Both procedures depend upon the sensitivity of the ultraviolet spectrum of oxyphenbutazone towards the pH of the solvent medium. In one procedure, the absorbance difference of oxyphenbutazone in an acid solvent (0.01 NHCl) and in an alkaline one (0.01 N NaOH) is measured at 254 nm; the mean percentage recovery amounts to 100.2±1.23 (p=0.05). The second procedure depends upon measurement of the absorbance difference of the drug in the acid solvent then in a pH 7-phosphate buffer at 262 nm; the mean percentage recovery amounts to 100.1±1.03 (p=0.05). The possible sources of interference in pharmaceutical formulations are studied and the two procedures are adapted to the analysis of some market preparations collected at random.

The clastogenicity of cisplatin, cis -diamminedichloroplatinum(II), an extensively used antitumor drug, has been studied employing (101/E1 × C3H/E1)F 1 mice, aged 12–14 weeks. Chromosomal aberrations were assessed in mitotic divisions of bone marrow cells and differentiating spermatogonia. The drug was tested at 3 doses, 0.5, 1.0 and 2.5 mg/kg and 1.0, 2.5 and 5.0 mg/kg, respectively, for bone marrow and spermatogonia. Cisplatin had a clastogenic effect which was dose-dependent in both cell types. The frequencies of aberrant cell increased non-linearly in bone marrow and the dose-response relationship could be best described by a linear-quadratic equation. At the highest dose the affected cells carried multiple aberrations. An average of 2.7 aberrations per aberrant cell was observed 12 h after treatment of the mice with 2.5 mg/kg of cisplatin. In differentiating spermatogonia the dose response for aberrant cells could be described by a linear equation. The damage to the individual affected cell was less dramatic than in bone marrow, averaging 1.4 aberrations per damaged cell at the highest dose tested. Gaps were excluded from these considerations but they generally also showed a dose-related increase. A quantitative comparison of the clastogenic response to cisplatin was based on the dose-response relationships using 2 criteria, the doubling dose and the dose of unit increase (DUI). For both comparisons the general conclusion was that bone marrow cells were twice as sensitive as differentiating spermatogonia to the clastogenic action of cisplatin.

Five nucleobase analogues with antiviral properties were tested for their mutagenic activity in his mutant strains TA 1535, TA 1537, TA 1538, TA98, and TA 100 of S. typhimurium by means of preincubation tests with and without metabolic activation by cell free fractions from mouse liver (S-9) and maize seedlings (S-14). In one bacterial strain 6-azathymine increased the revertant counts in the absence of metabolic activation systems. In the presence of S-9 mix, the same substance became mutagenic for another tester strain. Metabolic activation by S-14 resulted in weak mutagenicity of 5-azadihydrouracil in high concentrations. 6-Azauracil, 5-azauracil, and 5-azadihydro-1,3-diacetyluracil were without mutagenic activity in all Salmonella-strains used. Cyclophosphamide, like other standard promutagens, was shown to become mutagenic in the presence of S-14 plant fraction. Thus S-14 activation system besides the S-9 liver system can be employed in mutagenicity testing with microbial systems.

A new spectrophotoraetric method has been developed for the analysis of pheniramine maleate and chlorphenlramine maleste, based on their reaction with iron (III). Pheniramine maleate and ch lor pheniramine maleate were found to form a 2:1 complex with iron (III) with an average log. stability constant of 12.26 and 12.36, respectively. The iron (III) complexes of both drugs showed maximum absorption at 273 nm, at pH 5, with slopes equal to 0.710 and 0.898 for pheniramine maleate complex and chlorpheniramine maleate complex, respectively. The proposed method was used for the determination of pheniramine maleate and chlorpheniramine maleate in quantities ranging between 0.25 × 10−4 M to 2.5 × 10−4 M with mean percentage recoveries of 100.17 ± 1.09% and 100.00 ± 1.13% for both drugs, respectively. The results obtained were compared with that of the B.P. (1980) method.

Methotrexate, 4-amino-10-methyl folic acid, is one of the drugs belonging to the folic acid antagonists that is widely used for the treatment of cancer and psoriasis 1, 2

The first-derivative spectra of some metal complexes of danthron and phanquone show well defined, prominent peaks. This can be made the basis of a spectrophotometric technique for the determination of both danthron and phanquone. Two spectrophotometric. procedures are described. The first-derivative spectrophotometric technique, found to be more sensitive than the direct-absorbance method when the metal complex is weakly absorbing, can be applied to the determination of danthron, and phanquone both in pure form and in pharmaceutical formulations. Danthron can be determined in the range of 0.48–5.7 mg using metal complexes. Phanquone can be determined in the range of 0.42–2.08 mg using iron (II), and 3.78–11.34 mg using cobalt (II). The second procedure is a first-derivative spectrophotometry titration for the determination of 0.096–0.57 mg of danthron and 0.048–1.0 mg of phanquone using the standard metal ion- solutions as titrants.

The polarographic behavior of the widely used anti-inflammatory agent, oxyphenbutazone, was studied. It is determined polarographically by conversion to the nitroso derivative characterized by a cathodic, irreversible, diffusion-controlled wave. The method is applied to the determination of 2.5-10 mg/100 mL of oxyphenbutazone, with an accuracy of 99.9 ± 1.38%. By differential pulse polarographic analysis, as little as 10 ppm oxyphenbutazone can be determined with an accuracy of 99.70 ± 0.99% in pure powder and in some pharmaceutical formulations.

Acrylamide, known to induce dominant-lethal mutations (Shelby et al., 1986; Smith et al., 1986) and heritable translocations (Shelby et al., 1987) in rodent germ cells, was hitherto a questionable clastogen in rodent bone marrow (Shiraishi, 1978). Therefore, it was tested for chromosomal aberrations in mouse bone marrow cells, spermatogonia and by the micronucleus test. The intraperitoneally injected doses ranged from 50 to 150 mg/kg. In the chromosomal bone marrow test and the micronucleus assay positive results were obtained with acrylamide, and in the latter test the effect increased linearly with dose. Chromosomal aberrations were not induced in differentiating spermatogonia by the acute acrylamide treatment. Cisplatin was used as a positive control and gave the expected positive response in all 3 tests. The present results demonstrate that acrylamide is no exception among clastogens. It breaks chromosomes not only in mammalian germ cells but also in somatic cells.