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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.
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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.
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Anemia/epidemiologia , Malária Falciparum/epidemiologia , Magreza/epidemiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Malária/epidemiologia , Masculino , Desnutrição/epidemiologia , Plasmodium falciparum/fisiologia , Prevalência , Iêmen/epidemiologiaRESUMO
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.
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Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/terapia , Furanos/toxicidade , Nefropatias/terapia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Spirulina , Animais , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Antígeno Ki-67/metabolismo , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , RatosRESUMO
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.
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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.
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Resistência a Medicamentos/genética , Malária/transmissão , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Animais , Antimaláricos/farmacologia , Genótipo , Humanos , Malária/tratamento farmacológico , Modelos TeóricosRESUMO
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.
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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.
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Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Resistência a Medicamentos/genética , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Adulto , Idoso , Citalopram/administração & dosagem , Feminino , Genótipo , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Nortriptilina/administração & dosagem , Polimorfismo Genético , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
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.
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Peixes-Gato , Células Secretoras de Glucagon , Ilhotas Pancreáticas , Animais , Esôfago , Feminino , Insulina , Masculino , Pâncreas , Caracteres SexuaisRESUMO
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.
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Vasos Coronários/anatomia & histologia , Vasos Coronários/citologia , Animais , Tecido Conjuntivo , Cães , Células Endoteliais/citologia , Microscopia Eletrônica de Transmissão/veterinária , Miócitos de Músculo Liso/citologiaRESUMO
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.
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Transtorno Depressivo/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Ligação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RecidivaRESUMO
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.
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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.
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Antineoplásicos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Dextranos/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Fígado/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacosRESUMO
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.
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Comportamento do Adolescente/etnologia , Relações Pai-Filho/etnologia , Relações Mãe-Filho/etnologia , Poder Familiar/etnologia , Suicídio/etnologia , Adolescente , Adulto , Estudos Transversais , Egito/etnologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
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.
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Luteína/farmacologia , Traumatismo por Reperfusão/metabolismo , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Marcação In Situ das Extremidades Cortadas , Janus Quinase 1/metabolismo , Masculino , Malondialdeído/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Transcrição STAT3/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
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Antazolina/análise , Antialérgicos/análise , Imidazóis/análise , Descongestionantes Nasais/análise , Espectrofotometria/métodos , Combinação de Medicamentos , Controle de QualidadeRESUMO
Catechol-o-methyltransferase (COMT) is an enzyme that inactivates biologically active or toxic catechols. Previous studies have yielded inconsistent results on the relationship between erythrocyte COMT activity and affective disorders. Recently an amino acid change (Val-108-Met) of the COMT protein was shown to determine high- and low-activity alleles of the enzyme. Using polymerase chain reaction and the restriction enzyme NLaIII, we genotyped 107 patients with bipolar disorder, 62 with unipolar depression, and 121 controls. Neither bipolar nor unipolar patients differ significantly in the genotypic or allelic frequency from the control group. Even when the bipolar and unipolar patients were pooled into a single group, the distributions of both the genotypes and the alleles for the patient group were similar to those for the controls. We conclude that genetic variation that determines high and low activities of COMT does not have a major effect on the vulnerability to affective disorders in our sample.
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Catecol O-Metiltransferase/genética , Transtornos do Humor/genética , Adulto , Alelos , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Transtorno Depressivo/genética , Transtorno Depressivo/psicologia , Genótipo , Humanos , Transtornos do Humor/psicologia , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
Hepatic bile salt secretion and bile formation are essential functions of the mammalian liver, and the rate-limiting step of hepatocellular secretion of bile salts is canalicular secretion. Recently, the rat sister-of-p-glycoprotein/bile salt export pump (spgp/BSEP) was demonstrated to encode for the rat ATP-dependent canalicular bile salt export protein, and mutations of human BSEP were identified as the cause of PFIC 2. Since mouse models are vital for studies in hepatocellular transport and metabolism, cloning and characterization of the murine gene are essential. In this study, we have cloned a full-length, functional cDNA for the mBsep. The deduced amino acid sequence encodes for a 1321-amino-acid protein and is 94% similar to rat and 89% similar to human bsep. Western immunoblotting using an antibody directed against a carboxy-terminal peptide of mbsep protein reveals a 160kDa protein, which is highly enriched in mouse canalicular membranes. Transfection of mBSEP into Sf-9 insect cells or mammalian Balb-3T3 cells confers functional transport of the bile salt taurocholate. The mBsep mRNA is expressed in murine liver, but not in other tissues. Hepatic mBsep levels appear highly regulated, being markedly diminished in both LPS and estrogen models of cholestasis. These data are important for further murine studies of hepatocellular transport physiology and metabolism.
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Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Células 3T3 , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Sequência de Aminoácidos , Animais , Western Blotting , Linhagem Celular , Membrana Celular/metabolismo , Colagogos e Coleréticos/farmacocinética , Colestase/metabolismo , Clonagem Molecular , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Ratos , Homologia de Sequência de Aminoácidos , Ácido Taurocólico/farmacocinética , TransfecçãoRESUMO
Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamines, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphisms), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.
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Catecol O-Metiltransferase/genética , Desequilíbrio de Ligação , Polimorfismo Genético , Esquizofrenia/enzimologia , Esquizofrenia/genética , Substituição de Aminoácidos , Povo Asiático , Família , Impressão Genômica , Genótipo , Humanos , Japão , Reação em Cadeia da Polimerase , Transtornos Psicóticos/enzimologia , Transtornos Psicóticos/genética , Reino Unido , População BrancaRESUMO
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines such as adrenaline, noradrenaline, dopamine, and levodopa. Recently an amino acid change (Val-108-Met) of the COMT protein was found to determine high and low activity alleles of the COMT gene. We genotyped 109 Japanese patients with Parkinson's disease (PD) and 153 controls by using polymerase chain reaction (PCR) amplification and digestion by the restriction enzyme NlaIII. The frequency of low activity allele in the controls was 0.29, which was significantly different from that reported in Caucasians (0.50). When comparison was made between patients with PD and controls, homozygosity for the low activity allele was significantly more common among the patients than among the controls (P = 0.017; odds ratio, 2.8, 95% CI 1.2-6.5), suggesting that homozygosity for the low activity allele may increase susceptibility to PD.
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Alelos , Catecol O-Metiltransferase/genética , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Adulto , Etnicidade , Feminino , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
Reinvestigation of Onopordon ambiguum extract afforded a new eudesmane derivative 1, in addition to the known elemanoid derivative 2. The structures of both compounds were determined by spectroscopic techniques, including 1H-, 13C-NMR, DEPT, 1H-1H and 1H-13C COSY analysis.