Analysis of MiR-20b, MIR-197 markers for differentiation between forensic body fluids encountered in sexual assault cases.

Identifying body fluids can be a critical clue that aids in reconstructing the crime scene. Semen and vaginal fluid identification is crucial, especially in cases of sexual assault. The majority of forensic studies focused on identifying normal body fluids and neglected the expression variation of semen in pathology. To differentiate between vaginal fluids, fertile and infertile semen samples (oligospermia and azoospermia) using miR 20b and miR197. A total of 48 body fluid samples, divided as 16 vaginal fluids, 16 fertile semen, and 16 infertile semen samples (8 with oligospermia and 8 with azoospermia), were collected, and the expression levels of miR-20b and miR-197 were detected by the SYBR Green real-time quantitative PCR technique. Our results showed significant different expression of these miRNAs in normal semen compared to vaginal and infertile semen. Moreover, we designed a model based on Fisher's discriminant function to forecast the group affiliations of unidentified samples. With three novel equations, we were able to accurately distinguish between semen and vaginal fluid, fertile and infertile semen, and oligospermia and azoospermia semen samples with validation accuracy of 81.3%, 100%, and 100%, respectively. MiR-20b and miR-197 expression levels are efficient and appropriate markers to distinguish semen from vaginal fluid and to differentiate between fertile and infertile semen samples. However, the present study is a preliminary study based on clinical samples, and the potential role of these markers in differentiating real crime scene samples is still unknown, so we recommend further research to investigate these markers expression while using forensic samples.

Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition.

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

Unique localization of disseminated pancreas in the oesophagus of catfish (clarias gariepinus) with reference to sexual dimorphism.

BACKGROUND: The fish pancreas has been reported to be composed of two portions: compact and disseminated. However, little has been elucidated in catfish. The present study describes a unique localization of the disseminated pancreas in African catfish. METHODS: The sections were obtained and used for either routine histological examination following staining with haematoxylin and eosin (H & E), periodic acid-Schiff's, or were subjected to immunohistochemical staining for detection of both insulin-producing ß cells and glucagon-producing alpha cells. RESULTS: Our investigation showed that the pancreas of catfish consisted of both compact and disseminated portions. The compact pancreas was embedded in the mesenteric adipose tissue between the spleen, stomach and liver. However, the disseminated one showed unique localization in the tunica adventitia of the middle portion of the oesophagus. The pancreas consisted of two portions, exocrine and endocrine. Furthermore, in both types of pancreas, the female showed a significantly higher ratio for the endocrine islet area/pancreatic tissue area than that of the male and also a significantly higher ratio for both insulin- and glucagon-positive area/islet area in the female pancreas (compact and disseminated) than that of the male. IN CONCLUSION: The present study provides evidence on a unique localization of the disseminated pancreas in the oesophagus of catfish. Furthermore, we revealed sex-related difference in the endocrine portion in both pancreatic tissues with more development in the female. The study suggests that sex hormones could be contributed to such sexual dimorphism. However, further investigation is required to compare the degree of development during the spawning and resting seasons.

Uncomplicated falciparum malaria among schoolchildren in Bajil district of Hodeidah governorate, west of Yemen: association with anaemia and underweight.

BACKGROUND: Malaria, malnutrition and anaemia are major public health problems in Yemen, with Hodeidah being the most malaria-afflicted governorate. To address the lack of relevant studies, this study was conducted to determine the prevalence of Plasmodium falciparum and its relation to nutritional status and haematological indices among schoolchildren in Bajil district of Hodeidah governorate, west of Yemen. METHODS: A cross-sectional study was conducted among 400 schoolchildren selected randomly from four schools in Bajil district. Data about demographic characteristics, risk factors and anthropometric measurements of age, height and weight were collected. Duplicate thick and thin blood films were prepared, stained with Giemsa and examined microscopically for malaria parasites. The density of P. falciparum asexual stages was estimated on thick films. EDTA-blood samples were examined for the haematological indices of haemoglobin (Hb) and blood cell counts. RESULTS: Plasmodium falciparum was prevalent among 8.0% (32/400) of schoolchildren with a mean parasite density of 244.3 ± 299.3/µL of blood and most infections showing low-level parasitaemia, whereas Plasmodium vivax was detected in one child (0.25%). Residing near water collections was a significant independent predictor of falciparum malaria [adjusted odds ratio (AOR) = 2.6, 95.0% CI 1.20-5.72; p = 0.016] in schoolchildren. Mild anaemia was prevalent among more than half of P. falciparum-infected schoolchildren and significantly associated with falciparum malaria (AOR = 5.8, 95.0% CI 2.39-14.17; p < 0.001), with a mean Hb concentration of 10.7 ± 1.0 g/dL. Although the mean values of the total white blood cells, monocytes and platelets were significantly lower in infected than non-infected schoolchildren, they were within normal ranges. More than half of the children were malnourished, with stunting (39.3%) and underweight (36.0%) being the most prevalent forms of malnutrition; 6.3% of children were wasted. Underweight (AOR = 5.3, 95.0% CI 2.09-13.62; p < 0.001) but not stunting or wasting, was a significant predictor of falciparum malaria among schoolchildren. CONCLUSION: Asymptomatic falciparum malaria is prevalent among schoolchildren in Bajil district of Hodeidah Governorate, with predominance of low parasitaemic infections and significant association with mild anaemia and underweight. Residence near water collection is a significant predictor of infection with falciparum malaria among schoolchildren. Further studies among children with severe malaria and those with high parasite densities are recommended.

Protective effect of Spirulina platensis against physiological, ultrastructural and cell proliferation damage induced by furan in kidney and liver of rat.

The modulatory role of the Spirulina platensis (SP) against furan-induced (FU) hepatic and renal damage was assessed in this study. For achieving this, sixty rats were distributed into six groups: control group, SP-administered group (300 mg/kg b.wt orally for 28 days), a FU-intoxicated group (16 mg/kg b.wt, orally, daily for 28 days), protective co-treated group SP/F (administered SP 300 mg/kg b.wt, one week before, and concurrently with FU intoxication), therapeutic co-treated group FU/SP (administered SP 300 mg/kg b.wt, one week after FU intoxication for 28 days) and protective/therapeutic co-treated group SP/FU/SP (administered SP one week before and after, concurrently with FU intoxication). Subsequently, the biochemical responses and the histology of hepatic and renal tissues in treated rats were assessed. The results indicated that FU intoxication induced a significant hepato- and nephropathy represented by the elevation in the values of tissue injury biomarkers and reduction in protein levels. Histologically, a wide range of morphological, cytotoxic, inflammatory, and vascular alterations as well as downregulation in the immunoexpression of the proliferating cell nuclear antigen (PCNA) and the proliferation-associated nuclear antigen (Ki-67) were induced by FU intoxication. Oral SP administration, particularly in the protective/therapeutic co-treated group, markedly supressed the serum levels of the tissue injury biomarkers, diminished the inflammatory response, restored the cytotoxic alterations, upregulated the immunoexpression of PCNA and Ki-67, and restored the perturbed morphology of the hepatic and renal tissues. In conclusion, the obtained data demonstrated that SP co-administration elicits both protective and therapeutic potential against the FU-induced hepato- and nephropathy.

Histological and ultrastructural studies on the coronary artery of adult domestic dog (Canis familiaris).

The objective of this work was to study the histological structure of the dog's coronary artery by light and transmission electron microscope (TEM). The coronary artery consisted of three tunics: tunica intima, tunica media and tunica adventitia. The tunica intima consisted of endothelium rested directly on internal elastic lamina without the subendothelial connective tissue layer. The tunica media were composed of smooth muscle fibres interspersed with few elastic and collagen fibres. The tunica adventitia consisted of collagen and elastic fibres intermingled with fibroblast cells; it had vasa vasorum and nervi vasorum. Some histomorphometric measurements were performed and compared statistically. The ultrastructural study showed that the endothelial cells were communicated through complex junctions and characterised by filiform cytoplasmic processes passed through the opening of the underlying internal elastic membrane. The smooth muscle fibres of tunica media communicated with each other through cytoplasmic processes. The tunica adventitia showed minute non-myelinated nerve. This work revealed that the dog's coronary arteries are typical muscular arteries, which show little structural variations from that of other mammals.

Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models.

Effect of natural PAL-enzyme on the quality of egg white and mushroom flour and study its impact on the expression of PKU related genes and phenylalanine reduction in mice fed on.

PKU patients react to therapy with a low phenylalanine diet, but adherence to this diet is troublesome, subsequently the expansion of alternative ways is demand. Phenylalanine ammonia lyase (PAL) is one of this ways, which converts phenylalanine to harmless metabolites; trans-cinnamic acid and ammonia. In the current study, the extraction of PAL enzyme was used to investigate the efficiency for production of functional PKU egg white and mushroom flour with good quality by evaluation of colour characteristics, determination of phenylalanine concentrations and genetic materials expression of PKU related genes and DNA damage. Results indicated that the PAL enzyme treated of egg white and mushroom flour was stable colour and the calculated reduction per cent in phenylalanine concentration from female mice fed on untreated and PAL-treated samples was 22.77% in egg white and 31.37% in mushroom flour. Also, the results revealed that female mice fed on diet contained treated egg white exhibited low expression levels of PKU exons (3, 6, 7, 11, and 12) and low DNA damage which were similar to those in control mice.

Perception of Parental Bonds and Suicide Intent Among Egyptian Adolescents.

PROBLEM: Suicidal adolescents, compared to their nonsuicidal peers, tend to perceive their parents as less "caring" and more "controlling"-which characterizes the "affectionless control" parenting style. Research findings are inconsistent regarding the distinct influence of mother versus father parenting on youth suicide intent; moreover, the influence of parents' joint parenting styles on suicide intent has not been investigated. METHODS: Using a cross-sectional design and large sample (N = 150 youth, 13-21 years old), currently hospitalized in a treatment center in Egypt for a recent suicide attempt, data were collected using the Suicide Intent Scale, Parental Bonding Instrument, and Center for Epidemiologic Studies Depression Scale. FINDINGS: Seventy percent of youth reported high suicide intent. Mother and father parenting styles, assessed independently, were not associated with adolescent suicide intent. The joint effect of both parents' parenting style, however, was positively associated with suicide intent (Wald χ(2) = 8.79, p = .03). Suicide intent was stronger among adolescents who experienced neglectful compared with optimal parenting style (B = 1.93, Wald χ(2) = 4.28, p = .04). CONCLUSIONS: The findings have direct implications for mental health nursing interventions, signaling the critical need to engage both parents in family-based interventions to address youth suicidal behavior.

Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE.

Testicular ischemia reperfusion injury (tIRI) is considered as the underlying mechanism of testicular torsion, which can cause male infertility. tIRI-induced damage was investigated by assessing the gene expression of spermatogenesis master transcription factors (TFs) and that of major adhesion molecules of the blood-testis barrier. The effect of lutein, a hydroxyl carotenoid, in alleviating tIRI-induced damage was also studied. Male Sprague-Dawley rats were divided into three groups: sham, unilateral tIRI, and tIRI + lutein (0.2 mg/kg). tIRI was induced by occlusion of the testicular artery for 1 h, followed by 4 h of reperfusion. Lutein was injected 15 min after the start of ischemia. Histological analysis and real-time polymerase chain reaction revealed significant decreases in tissue biopsy scores, reduced seminiferous tubule diameters, and downregulated the mRNA expression of the TFs cAMP-responsive element modulator (CREM), TATA box-binding protein-related factor 2 (TRF2), and regulatory factor X 2 (RFX2) compared with the sham group. Lutein treatment reversed these effects. The mRNA expression of the adhesion molecules N-cadherin, nectin-2, claudin-11, occludin, and connexin-43 was significantly downregulated during tIRI, but this change was prevented by lutein treatment. In addition, lutein normalized the tIRI-induced increase in total antioxidant capacity, increased malondialdehyde (MDA) levels, augmented number of TdT-mediated dUTP-X nick-end labeling (TUNEL)-positive nuclei, and activated caspase-8 pathway. The components of survivor activating factor enhancement (SAFE) were also activated during tIRI. Increased tissue expression of TNF-α and its receptor, TNFR1, was accompanied by increased phosphorylation of Janus kinase (JAK) and STAT3, which was prevented by lutein treatment. Our findings suggested that tIRI-induced spermatogenic damage may involve modulation of the SAFE pathway and could benefit from lutein treatment.

Comparative study between recent methods manipulating ratio spectra and classical methods based on two-wavelength selection for the determination of binary mixture of antazoline hydrochloride and tetryzoline hydrochloride.

A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating ratio spectra (ratio difference method and first derivative of ratio spectra method) for simultaneous determination of Antazoline hydrochloride (AN) and Tetryzoline hydrochloride (TZ) in their combined pharmaceutical formulation and in the presence of benzalkonium chloride as a preservative without preliminary separation. The dual wavelength method depends on choosing two wavelengths for each drug in a way so that the difference in absorbance at those two wavelengths is zero for the other drug. While Vierordt's method, is based upon measuring the absorbance and the absorptivity values of the two drugs at their λ(max) (248.0 and 219.0 nm for AN and TZ, respectively), followed by substitution in the corresponding Vierordt's equation. Recent methods manipulating ratio spectra depend on either measuring the difference in amplitudes of ratio spectra between 255.5 and 269.5 nm for AN and 220.0 and 273.0 nm for TZ in case of ratio difference method or computing first derivative of the ratio spectra for each drug then measuring the peak amplitude at 250.0 nm for AN and at 224.0 nm for TZ in case of first derivative of ratio spectrophotometry. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. All methods were applied successfully for the determination of the selected drugs in their combined dosage form proving that the classical spectrophotometric methods can still be used successfully in analysis of binary mixture using minimal data manipulation rather than recent methods which require relatively more steps. Furthermore, validation of the proposed methods was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that the methods can be competitively applied in quality control laboratories.

Detection of low-intensity Schistosoma mansoni infection by Percoll sedimentation and real-time PCR techniques in a low-endemicity Egyptian setting.

OBJECTIVE: To evaluate the performance of Percoll sedimentation and real-time polymerase chain reaction (PCR) for the detection of S. mansoni cases previously tested as negative by Kato-Katz technique in two low-endemic areas in Alexandria, Egypt, Abis 4 and 8 villages. METHODS: Stool samples of 824 primary schoolchildren were examined by Kato-Katz technique (three slides of 41.7 mg each). After obtaining the results of this survey, stool samples were recollected from a subset of 150 students, who gave negative results after Kato-Katz. These samples were microscopically examined after the concentration with Percoll technique. Part of the 150 negative stool samples and five positive samples (used as controls) were kept at -20 °C and further processed by SYBR Green PCR. RESULTS: Prevalence of S. mansoni infection as determined by three Kato-Katz thick smears was 1.82% (15 cases). Three more cases tested positive by Percoll sedimentation among the 150 samples that were negative by Kato-Katz. Specific amplification by SYBR Green PCR was noted in all positive controls and in three cases of Kato-Katz-negative samples, two of which were also positive by Percoll. CONCLUSION: Percoll sedimentation and SYBR Green PCR proved useful in detecting low-intensity S. mansoni infections in low-endemicity areas in Egypt.

Measuring resistant-genotype transmission of malaria parasites: challenges and prospects.

Increased gametocytemia in infections with resistant strains of Plasmodium species and their enhanced transmissibility are a matter of concern in planning and evaluating the impact of malaria control strategies. Various studies have determined weekly gametocyte carriage in response to antimalarial drugs in clinical trials. The advent of molecular biology techniques makes it easy to detect and quantify gametocytes, the stages responsible for transmission, and to detect resistant genotypes of the parasite. With the validation of molecular markers of resistance to certain antimalarial drugs, there is a need to devise a simpler formula that could be used with these epidemiological antimalarial resistance tools. Theoretical models for transmission of resistant malaria parasites are difficult to deploy in epidemiological studies. Therefore, devising a simple formula that determines the potential resistant-genotype transmission of malaria parasites should provide further insights into understanding the spread of drug resistance. The present perspective discusses gametocytogenesis in the context of antimalarial treatment and drug resistance. It also highlights the difficulties in applying the available theoretical models of drug resistance transmission and suggests Rashad's devised formula that could perhaps be used in determining potentially transmissible resistant genotypes as well as in mapping areas with high potential risk for the transmission of drug-resistant malaria. The suggested formula makes use of the data on gametocytes and resistant genotypes of malaria parasites, detected by molecular techniques in a certain geographical area within a particular point in time, to calculate the potential risk of resistant genotype transmission.

Prevailing Plasmodium falciparum dihydrofolate reductase 108-asparagine in Hodeidah, Yemen: a questionable sulfadoxine-pyrimethamine partner within the artemisinin-based combination therapy.

Given that the evolution and spread of resistance to sulfadoxine-pyrimethamine (SP) have been documented at a quick pace worldwide, the present study investigated the mutant Plasmodium falciparum dihydrofolate reductase 108-asparagine (dhfr 108 N) as a key marker of resistance to the combination among parasite isolates from Hodeidah. The association of parasitologic indices with the dhfr 108 N mutant allele was also studied. Ninety patients with microscopically confirmed P. falciparum infection from Hodeidah were included in the present study. Polymerase chain reaction-restriction fragment length polymorphism approach was adopted for the molecular detection of this marker. The dhfr 108 N was detected among about 61% of P. falciparum isolates, in its pure and mixed-type forms, from Hodeidah. Age, gender and residence of patients were not significant predictors for the presence of the mutant allele among parasite isolates. In contrast, a history of malaria and antimalarial drug intake in the year preceding the study as well as frequent antimalarial drug intake were significantly associated with this mutant allele. The high frequency of dhfr 108 N among parasites isolates makes the role of SP questionable as a partner with outstanding effectiveness within the ACT, at least, in the near future. SP plus artesunate should be monitored for its antimalarial efficacy at regular intervals, preferably through the molecular detection of resistance-associated mutations.

Mutant Plasmodium falciparum chloroquine resistance transporter in Hodeidah, Yemen: association with parasitologic indices and treatment-seeking behaviors.

Malaria still represents a major health problem in Yemen, particularly in Hodeidah, despite continuing efforts to eliminate it. With the absence of clinically proven vaccines, chemotherapy with antimalarials is still greatly needed. Chloroquine (CQ) has been popular as the drug of choice for malaria control. However, Plasmodium falciparum resistance to CQ has been one of the main obstacles in malaria control and elimination. Although CQ is no longer the recommended antimalarial chemotherapy, it has remained the number one over-the-counter antimalarial drug in many endemic areas, including Yemen, and is still used for self-medication. In addition, promising reports on CQ efficacy reversal in many African countries brought it again into the scene. This has led to a growing interest in the possibility of its re-introduction, particularly with the concerns raised about the parasite resistance to artemisinin-based combination therapies. Therefore, the present study aimed at analyzing the CQ-associated pfcrt 76T mutation in P. falciparum isolates from patients with uncomplicated falciparum malaria in Hodeidah, west of Yemen. The association of treatment-seeking behaviors and antimalarial drug use with the pfcrt 76T mutant allele was also studied. It was revealed that there is still a sustained high frequency of this molecular marker among parasite isolates associated with younger age, decreased parasite density and the presence of gametocytes in blood. Delay in seeking treatment and frequent use of antimalarials were the behaviors significantly associated with the presence of the pfcrt 76T mutant allele among patients reporting a history of malaria treatment.

Sulfadoxine-pyrimethamine resistance in Plasmodium falciparum: a zoomed image at the molecular level within a geographic context.

Antimalarial chemotherapy is one of the main pillars in the prevention and control of malaria. Following widespread resistance of Plasmodium falciparum to chloroquine, sulfadoxine-pyrimethamine came to the scene as an alternative to the cheap and well-tolerated chloroquine. However, widespread resistance to sulfadoxine-pyrimethamine has been documented. In vivo efficacy tests are the gold standard for assessing drug resistance and treatment failure. However, they have many disadvantages, such as influence of host immunity and drug pharmacokinetics. In vitro tests of antimalarial drug efficacy also have many technical difficulties. Molecular markers of resistance have emerged as epidemiologic tools to investigate antimalarial drug resistance even before becoming clinically evident. Mutations in P. falciparum dihydrofolate reductase and dihydrofolate synthase have been extensively studied as molecular markers for resistance to pyrimethamine and sulfadoxine, respectively. This review highlights the resistance of P. falciparum at the molecular level presenting both supporting and opposing studies on the utility of molecular markers.

Protective role of selenium against over-expression of cancer-related apoptotic genes induced by o-cresol in rats.

Cresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.

No association with the 5,10-methylenetetrahydrofolate reductase gene and major depressive disorder: results of the depression case control (DeCC) study and a meta-analysis.

Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta-analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations. This may parallel a similar reduction in 5-methyltetrahydrofolate in the CNS, leading to a potential reduction in monoamine neurotransmitter function and an elevated risk of depressive disorder. To test the hypothesis that the MTHFR C677T polymorphism is involved in the predisposition to MDD, we conducted an association study of 1,222 patients with recurrent MDD and 835 control subjects. This allows 99% power to detect an effect of the size reported in the study of Bjelland et al. 2003, however no significant differences in genotype or allele frequencies between depressive patients and controls were observed. This was the case in the sample as a whole, and when females and males were considered separately. Our findings suggest that the MTHFR C677T polymorphism is not involved in the etiology of clinically significant recurrent MDD.

Polyol monoterpenes and sesquiterpene lactones from the Pacific Northwest plant Artemisia suksdorfii.

Five new polyol monoterpenes (1-5) and seven new sesquiterpene lactones (6-12), along with five previously identified compounds, were isolated from the aerial parts of Artemisia suksdorfii. The structures of the new compounds were established by high-field NMR techniques (1H, 13C, 1H-1H DEPT, COSY, HMQC, and HMBC) and in case of 6 confirmed by X-ray analysis.