Effect of Bioabsorbable Poly (dl-Lactide ε-Caprolactone) on Healing of Experimentally Injured Acute Traumatic Middle Ear Mucosa Damage.

BACKGROUND: Postoperative adhesion is an important complication after middle-ear surgeries. Although many materials have been tried to prevent this complication, the use of Poly (dl-lactide ε-caprolactone) as an anti-adhesive material after middle-ear surgery has not yet been reported. The aim of this study was to evaluate the anti-adhesive effect of poly (dl-lactide ε-caprolactone) on the ears of rats with middle-ear mucosa damage. METHODS: In our study, 14 Wistar albino rats and 28 ears in total were used. The rats were randomly divided into 4 groups. Middle ear mucosa damage was performed in all groups with a transcanal approach under otomicroscopy in sterile conditions. The effects of poly (dl-lactide ε-caprolactone), silicone sheet, and absorbable gelatin sponge were compared histologically with the secondary healing group. In addition, hearing evaluation was performed before the procedure and on the 28th postoperative day. RESULTS: No significant difference was observed in transient otoacoustic emission and distortion product otoacoustic emissions tests performed before and after the surgical procedure when the groups were compared. While adhesion was observed in the tympanic membrane in the absorbable gelatin sponge group, no adhesion was observed in the other groups. In the absorbable gelatin sponge group, increased fibroblastic activity, inflammation, and neovascularization were observed in the middle-ear mucosa. No significant difference was observed in silicone sheet, poly (dl-lactide ε-caprolactone), and control groups in terms of fibroblastic activity, inflammation, and neovascularization. CONCLUSION: It can be concluded that absorbable poly (dl-lactide ε-caprolactone) is nonototoxic and biocompatible with the rat's middle ear cavity by short-term evaluation.

The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy

Purpose Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. Methods After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. Results Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. Conclusion Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population (AU)

The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. METHODS: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. RESULTS: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. CONCLUSION: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.

Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study.

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.

Immunotherapeutic role of cabazitaxel treatment in the activation of TLR3 signalling in metastatic castration-resistant prostate cancer in vitro.

BACKGROUND: The activation of toll like receptors (TLR) potentially affect the inflammatory tumor microenvironment and thus is associated with tumor growth or inhibition. Cabazitaxel (CAB) has been effectively used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the immune regulatory role of CAB in the tumor microenvironment is not clear. In this context, we for the first time assessed the immunotherapeutic role of CAB in the TLR3 signalling following activation of Poly I:C in mCRPC cells. METHODS AND RESULTS: The cytotoxic and apoptotic effects of CAB with the induction of Poly I:C were determined by WST-1, Annexin V, acridine orange, RT-PCR analysis, ELISA assay and immunofluorescence staining in DU-145 mCRPC and HUVEC control cells. Our findings showed that CAB treatment with Poly I:C significantly suppressed the proliferation of DU-145 cells through the induction of apoptosis and caspase activation. Additionally, higher concentration of CAB mediated the activation of TLR3 via increased cytoplasmic and nuclear expression of TLR3, TICAM-1 and IRF-3 in mCRPC cells. CONCLUSIONS: Co-treatment of CAB and Poly I:C was more effective in mCRPC cells with less toxicity in control cells. However, further investigations are required to elucidate the molecular mechanisms of TLRs signalling upon CAB treatment at the molecular level to further validate the immunotherapeutic efficacy of CAB in mCRPC.

Regulation of valproic acid induced EMT by AKT/GSK3ß/ß-catenin signaling pathway in triple negative breast cancer.

Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. The epithelial-to-mesenchymal transition (EMT) mediating by different signaling cascade can be a potential target in aggressive human cancers. Therefore, we aimed to clarified the unravel relationship between AKT/GSK3ß/ß-catenin signalling pathway and VPA-induced EMT in triple negative breast cancer (TNBC). The cytotoxicity of VPA in MDA-MB-231 TNBC and MCF-10A control cells was evaluated. Alterations in the expression levels of Snail, E-cadherin, AKT, GSK3ß, ß-catenin were analyzed by RT-PCR. Additionally, Annexin V, cell cycle and wound healing assays were performed. Our results showed that VPA remarkably inhibited the growth of TNBC cell and triggered apoptotic cell death through G0/G1 arrest. Furthermore, VPA increased cell migration and activated the EMT process through significantly increasing Snail expression and in turn downregulation of E-cadherin and GKS3ß levels. However, the level of AKT and ß-catenin was reduced after treatment of VPA. Our data showed that VPA induced EMT process and cell migration in TNBC cells. However, AKT/GSK3ß/ß-catenin signaling pathway did not mediate EMT activation.

Histological Study of The Healing of Traumatic Tympanic Membrane Perforation After Vivosorb and Epifilm Application.

BACKGROUND: Untreated traumatic tympanic membrane perforations (TMPs) may lead to permanent perforations and hearing loss. There are many materials that have been previously used for repairing the TMPs. AIMS AND OBJECTIVES: The purpose of this study is to evaluate the clinical and histological effects of Vivosorb (Vv) and Epifilm on healing of TMPs in a rat model. MATERIAL AND METHODS: The posterior-inferior quadrant of the tympanic membranes (TMs) in right ears of 14 rats was perforated using a 20-g needle and then the animals were randomly divided into 2 equal groups (n = 7). The perforated right TMs were treated with either Vv (Vv group) or Epifilm (Ep group). The left TMs of 7 rats were perforated in same way and allowed to close spontaneously without any topical material applications (spontaneous closure group as sham control, SC). The left tympanic membranes of the other 7 rats were not perforated and used as normal controls (NC group). On postoperative 15th day, tympanic bullas were extracted from killed rats and examined morphometrically and histopathologically. RESULTS: Perforation closure rate was 85.7% (6/7) in both Vv and SC groups. Perforations of Ep group closed in 7/7 (100%) ears. The thicknesses of the perforated membranes were increased in SC and especially Vv groups. Also, connective tissue fibrosis, blood clots, and epithelial degenerations were detected in SC and Vv groups. The mean fibroblastic reaction scores of Vv, Ep, and SC groups were 2.14(+), 0.57(+), and 1.71(+) respectively, on comparison with NC group. The mean neovascularization score was 1.42(+) in Vv group, 0.14(+) in Ep group, and 0.57(+) in SC group. CONCLUSION AND SIGNIFICANCE: Vivosorb and especially Epifilm can improve the healing process in traumatic TMPs and additionally, Epifilm might be more preferred for the treatment of TMPs because of causing lesser fibrosis.

Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer.

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin's therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation.

The effect of chronic stress and obesity on sperm quality and testis histology in male rats; a morphometric and immunohistochemical study.

OBJECTIVE: Stress and obesity lead structural and functional abnormalities in many organs. This research investigated the effect of these two risk factors on sperm parameters and histologic structure of testis in rat model. MATERIALS AND METHODS: Twenty-four male rats were divided into four groups with six rats in each group as control, stress, obesity, and stress-obesity groups. The rats of obesity and stress-obesity groups were fed high-fat diet for 12-week and obesity was created. Control and stress groups were given standard rat chow for the same time. Through last 4-week, stress and stress-obesity groups were applied to chronic mild stress procedure. At the end of the experiment, epididymal sperm was collected from vas deferens and testes were harvested from sacrificed animals. Sperm samples were evaluated in terms of concentration and motility by using Makler Chamber. Sperm smears were stained with Eosin-Y stain for morphological evaluation, and also histochemically for GABA transporter-1 (GAT1) expression assessment. Testis sections were dyed with Hematoxylin-Eosin and Johnsen scores were assessed. GAT1 expression was detected in testis sections by immunohistochemistry, and TUNEL method was used for determining apoptosis in testis. RESULTS: In comparison with the control samples in stress, obesity, and stress-obesity groups sperm concentration and motility decreased, and also the number of sperm with abnormal morphology increased. Stress, obesity, and stress-obesity groups showed a significantly decreased in sperm concentration and motility in comparison with the control group, and also in these groups had significantly increased number of abnormal sperm compared to control. Additionally, the testicular structure was deteriorated, and Johnsen scores decreased. And also GAT1 expression and apoptosis were prominent. These negative results, especially, testicular weight, sperm concentration, and Johnsen score were more observed in the stress-obesity group. CONCLUSIONS: Stress and obesity may induce male infertility by disrupting both sperm quality and testis histology. When stress and obesity are coexisting, these adverse effects are more severe. And also, increased GAT1 expression may be associated with these effects.

Does cigarette smoke exposure lead to histopathological alterations in the olfactory epithelium? An electron microscopic study on a rat model.

OBJECTIVE: This study was conducted to examine the influence of smoke exposure of variable duration on the ultrastructure of and histopathologic and morphologic alterations in the olfactory epithelium. METHODS: A total of 24 Wistar albino rats were randomly assigned to three groups and fed a standard rat chow and tap water. Experimental rats in groups I and II were exposed to cigarette smoke in a glass cabin over a period of 2 months for 5 or 15 min, respectively, four times daily; control rats (group III) were not exposed to cigarette smoke. After dissection, all tissue specimens were processed using routine procedures for TEM. RESULTS: Groups I and II exhibited the presence of intraepithelial inflammatory cells and especially deep invaginations in the nuclear membrane of supporting cells. Extended intercellular spaces, cytoplasmic protrusions on the apical surface of supporting cells, atrophy of microvilli and olfactory neuron cilia as well as numerous electron-dense granular structures and lysosome-like structures were observed to an increasing degree from group I to group II. Particularly in group II, both supporting cells and olfactory neurons exhibited a cytoplasmic edema, mitochondrial degeneration, and numerous vacuolar structures, as well as apoptotic and minimal necrotic changes. In this group, hyperplasia of basal cells was also observed. CONCLUSION: Our electron microscopic findings show that cigarette smoke leads to toxic degenerative changes in the rat olfactory mucosa.

Gender perspective on the factors predicting recycling behavior: Implications from the theory of planned behavior.

This study aimed to assess the role of some socio-psychological attributes in explaining recycling behavior of Turkish university community from a gender perspective within the context of the theory of planned behavior with an additional variable (past experience). The recycling behavior of whole sample, females and males, has been examined in 3 sessions -depending on the arguments that explain gendered pattern of private and public environmental behavior and sticking to the fact why females' stronger environmental values, beliefs, and attitudes do not translate consistently into greater engagement in public behavior. As a result of model runs, different variables shaping intention for behavior have been found, namely perceived behavior control for females and past behavior for males. Due to the low percent of the variance in explaining recycling behavior of females, they have been identified as the ones who do not carry out intentions (non-recyclers). Since intentions alone are capable of identifying recyclers accurately but not non-recyclers, there may be other factors to be considered to understand the reason for females not carrying out the intentions. The results of descriptive statistics supported the identification by attitudes toward recycling. Female attitudes were innate (recycling is good, necessary, useful and sensitive), whereas those of males were learnt (recycling is healthy, valuable and correct). Thus, it has been concluded that males' intention for recycling is shaped by their past behavior and the conclusion is supported by males having learnt attitude toward recycling whereas females' lack of intention for recycling is shaped by their perceived behavior control and is supported by their innate attitude for recycling. All in all, the results of the present study provide further support for the utility of the TPB as a model of behavioral prediction and concur with other studies examining the utility of the TPB in the context of recycling.

Avaliação da memória sob anestesia venosa total / The assessment of memory under total intravenous anesthesia / Evaluación de la memoria bajo anestesia venosa total

JUSTIFICATIVA E OBJETIVOS: Neste estudo, objetivamos avaliar a memória implícita e explícita em pacientes submetidos à cirurgia abdominal sob anestesia venosa total (AVT) com propofol e remifentanil, na qual o nível de anestesia foi controlado pelo monitoramento do índice bispectral (BIS). MÉTODO: Anestesia venosa total foi administrada a 60 pacientes adultos para obter níveis de BIS de 40-60. Os pacientes foram randomicamente divididos em três grupos, de acordo com as gravações que ouviram. Os pacientes do grupo categoria (CT) ouviram uma fita gravada contendo cinco nomes de animais. Os pacientes do grupo recordar palavras (RP) ouviram uma fita gravada contendo cinco palavras de frequência média na língua turca, depois de adaptadas. Os pacientes do grupo controle (GC) ouviram os sons do mar até o fim da cirurgia. Duas horas após a cirurgia, os testes foram administrados a cada paciente na sala de recuperação para avaliar a memória. RESULTADOS: Houve uma diferença entre os escores dos grupos CT e GC no Miniexame do Estado Mental (MMSE); todos os escores foram > 20. Os resultados dos testes de categoria e recordar palavras, aplicados para avaliar a memória implícita, não foram estatisticamente diferentes entre os grupos. Não houve evidência de memória implícita em nenhum dos pacientes. Um paciente lembrou-se de ouvir "o som de água" como uma prova de memória explícita. Onze pacientes declararam não ter sonhado. CONCLUSÕES: Apesar de não termos encontrado nenhuma evidência de memória implícita sob anestesia adequada com AVT, um paciente apresentou memória explícita. Embora a profundidade adequada da anestesia fornecida pelo monitoramento do BIS corrobore nossos resultados para a memória implícita, ela não explica os resultados para a memória explícita.

BACKGROUND AND OBJECTIVES: In this study, we aimed to assess implicit and explicit memory in patients who had abdominal surgery under total intravenous anesthesia (TIVA) with propofol and remifentanil, in which anesthesia level was controlled by bispectral index (BIS) monitoring. METHOD: Total intravenous anesthesia was administered to 60 adult patients, to obtain BIS levels of 40-60. Patients were randomly allocated to three groups according to tapes they listened to. Patients in the category group (CT) listened to a tape containing five animal names. Patients in the word recognition group (WM) listened to a tape containing five intermediate-frequency words, adapted into Turkish. Patients in the control group (CG) listened to sea sounds until the end of surgery. Two hours after surgery, tests were administered to each patient in the recovery room to assess memory. RESULTS: There was a difference between the CT and CG groups in their Mini-Mental State Examination scores, all values were > 20. The results of the category and word recognition tests that were applied to assess implicit memory were not statistically different among the groups. There was no evidence of implicit memory in any of the patients. One patient remembered hearing 'the sound of water' as a proof of explicit memory. Eleven patients said they had dreamt. CONCLUSIONS: Although no evidence of implicit memory under adequate anesthesia with TIVA was found, one patient showed explicit memory. Although adequate depth of anesthesia provided by BIS monitoring supports our implicit memory results, it does not explain the explicit memory results.

JUSTIFICATIVA Y OBJETIVOS: En este estudio evaluamos la memoria implícita y explícita en pacientes sometidos a la cirugía abdominal bajo anestesia venosa total (AVT), con propofol y remifentanilo, en la cual el nivel de anestesia fue controlado por el monitoreo del índice bispectral (BIS). MÉTODO: Anestesia venosa total que fue administrada a 60 pacientes adultos para obtener niveles de BIS de 40-60. Los pacientes fueron aleatoriamente divididos en tres grupos de acuerdo con las grabaciones que oyeron. Los pacientes del grupo categoría (CT) oyeron una cinta grabada que contenía cinco nombres de animales. Los pacientes del grupo recordar palabras (RP), escucharon una cinta grabada que contenía cinco palabras de frecuencia media en lengua turca, después de haber sido adaptadas. Los pacientes del grupo control (GC) oyeron los sonidos del mar hasta el final de la cirugía. Dos horas después de la cirugía, los test fueron administrados a cada paciente en la sala de recuperación para evaluar la memoria. RESULTADOS: Hubo una diferencia entre las puntuaciones de los grupos CT y GC en el Mini Examen del Estado Mental (MMSE) y todas las puntuaciones fueron > 20. Los resultados de los test de categoría y recordar palabras aplicados para evaluar la memoria implícita no fueron estadísticamente diferentes entre los grupos. No hubo evidencia de memoria implícita en ninguno de los pacientes. Un paciente recordó escuchar "el sonido del agua" como una prueba de memoria explícita. Once pacientes dijeron que no habían soñado. CONCLUSIONES: A pesar de no haber encontrado ninguna evidencia de memoria implícita bajo anestesia adecuada con AVT, un paciente tuvo memoria explícita. Aunque la profundidad adecuada de la anestesia suministrada por el monitoreo del BIS corrobore nuestros resultados para la memoria implícita, ella no explica los resultados para la memoria explícita.

The assessment of memory under total intravenous anesthesia.

BACKGROUND AND OBJECTIVES: In this study, we aimed to assess implicit and explicit memory in patients who had abdominal surgery under total intravenous anesthesia (TIVA) with propofol and remifentanil, in which anesthesia level was controlled by bispectral index (BIS) monitoring. METHOD: Total intravenous anesthesia was administered to 60 adult patients, to obtain BIS levels of 40-60. Patients were randomly allocated to three groups according to tapes they listened to. Patients in the category group (CT) listened to a tape containing five animal names. Patients in the word recognition group (WM) listened to a tape containing five intermediate-frequency words, adapted into Turkish. Patients in the control group (CG) listened to sea sounds until the end of surgery. Two hours after surgery, tests were administered to each patient in the recovery room to assess memory. RESULTS: There was a difference between the CT and CG groups in their Mini-Mental State Examination scores, all values were > 20. The results of the category and word recognition tests that were applied to assess implicit memory were not statistically different among the groups. There was no evidence of implicit memory in any of the patients. One patient remembered hearing 'the sound of water' as a proof of explicit memory. Eleven patients said they had dreamt. CONCLUSIONS: Although no evidence of implicit memory under adequate anesthesia with TIVA was found, one patient showed explicit memory. Although adequate depth of anesthesia provided by BIS monitoring supports our implicit memory results, it does not explain the explicit memory results.

Comparison of etomidate-remifentanil and propofol-remifentanil sedation in patients scheduled for colonoscopy.

OBJECTIVE: The aim of the study was to compare haemodynamic responses, recovery and discharge times, and physician satisfaction of etomidate-remifentanil and propofol-remifentanil combinations in patients undergoing elective colonoscopy. METHODS: Sixty patients, aged 18-65 years, scheduled for elective colonoscopy under sedation were prospectively randomized, double blind for the study. Two minutes after the beginning of a continuous remifentanil infusion (0.1 microg kg(-1) min(-1)), etomidate or propofol were administered. Patients in the etomidate group received a 0.05 mg kg(-1) maintenance dose of etomidate after an initial dose of 0.1 mg kg(-1), and patients in the propofol group received a 0.25 mg kg(-1) maintenance dose of propofol after an initial dose of 0.5 mg kg(-1) in order to have a Ramsay sedation score of 3-4. Basal values of heart rate, mean arterial pressure, oxygen saturation, respiratory rate and Ramsay sedation score were recorded. Values were recorded every 2 min for the first 10 min and every 5 min thereafter, until the completion of the procedure. RESULTS: Mean arterial pressure was lower at 4, 6, 8, 10, 15, 20 and 25 min in the propofol group (P = 0.001). Mean respiratory rate in the propofol group at 6, 8, 10, 15, 20, 25 min was also lower (P < 0.05). The incidence of apnoea and hypotension was significantly lower in the etomidate group (P < 0.001). Arrival time into the postoperative care unit and recovery time were shorter in the etomidate group (P = 0.001, P = 0.01, respectively). Physician satisfaction in both groups was similar. CONCLUSION: Etomidate-remifentanil administration for sedation and analgesia during colonoscopy resulted in more stable haemodynamic responses and shorter recovery and discharge times.

Pharmacogenomic genotyping methodologies.

"Personalized medicine" based on an individual's genetic makeup is slowly becoming a reality as pharmacogenomics moves from the research setting to the clinical laboratory. Concordance studies between genotype and phenotype have shown that inherited mutations in several key drug-metabolizing enzymes, such as cytochrome P450 ( CYP ) 2D6 , 2C9 , and 2C19 , result in several distinct phenotypes that lead to different individual responses following drug administration. One of the major driving forces behind pharmacogenomics and its ability to be used effectively are the technologies that are available. A beneficial genotyping test must identify most or all of the mutations that have a significant impact on the expression or function of drug-metabolizing enzymes, transporter proteins, and/or drug receptors. Selection of the appropriate technology will be based on several issues, including prior knowledge of the mutation/polymorphism, sensitivity/specificity, sample requirements, and cost. Since the future volume of pharmacogenomic testing is anticipated to be large, automation of pharmacogenomics will also become increasingly important. This paper provides an overview of current technologies available for assessing polymorphisms on a small- to large-scale basis.

Pharmacogenomics as molecular autopsy for postmortem forensic toxicology: genotyping cytochrome P450 2D6 for oxycodone cases.

Pharmacogenomics, the study of the impact of heritable traits on pharmacology and toxicology, may serve as an adjunct for certifying opioid fatalities. Oxycodone, frequently prescribed for the relief of moderate to severe pain, is metabolized by cytochrome P450 (CYP) 2D6, encoded by a polymorphic gene with three mutations (*3, *4, and *5) with a combined 95% allelic frequency and about 10% prevalence. Individuals with variant alleles are more susceptible to oxycodone toxicity. By assessing the prevalence of CYP2D6 polymorphisms and covariables, we hypothesized that oxycodone fatality may be partially due to poor drug metabolism caused by CYP2D6 variant alleles. From the Milwaukee County Medical Examiner's Office (MCMEO), a retrospective analysis of 15 oxycodone cases was followed by genotyping blood samples for the variant alleles by conventional and real-time PCRs. Institutional Review Board approval was obtained. Oxycodone, extracted from blood and/or urine, was quantitated by GC-MS. The results show two homozygous for 2D6*4 and four heterozygous for 2D6*4. The MCMEO was not significantly different from those in the control group (n = 26) (p > 0.05, Fisher's Exact Test). However, genotyping CYP2D6 provided a more definitive interpretation of the oxycodone toxicity in four cases. Therefore, pharmacogenomics may serve as an adjunct in the determination of the cause and manner of death in forensic toxicology and a pharmacogenomic algorithm for genotyping has been proposed.