Medical Biology

There is a need in small group teaching for a readable module that provides a balanced treatment of the four main areas of medical microbiology-bacteriology, mycology, virology and parasitology. it need not be encyclopedic in scope nor didactic, but it should emphasize principles and concepts. any existing gaps in this type of presentation are, of course, left for the student to fill. Some subject material has been exluded. An example is a chapter on laboratory procedures including PCR for rapid bacterial and viral diagnosis. The discussion of bacterial sexually transmitted diseases does not cover gonococcal infections. This is not a serious matter because the tutor can assign the topic to the students. Moreover, we have reluctantly ommited a separate chapter on anaerobic bacteria.

Abstrak Allelopathy is the compound released by the plants(exxample: blady grass) to the environmental and where another plants is living and could abstruct or extinguish to another plants. aimed to study alelopati effect extraction from Imperata cylindrica, Acacia mangium, Leucaena leucocephala, Muntingia calabura and Manihot glaziovii on the growth of corn and green beans and tomato. Alelopati extract used to see changes in planth growth. Experiments were carried out for 4 weeks. Tool used is polybag, filter paper, soil and fertilizer. The result obtained are residues can inhibit the growth of corn and green beans. Alelopati contains treponoid, flavonoid, and phenolic compound resulting acid synthesis inhibition ketoglutarat. There are several types of residues that are inhibiting subtance and there are also plants that are growing.

Abstrak Thermogulasi merupakan proses yang terjadi dalam tubuh hewan untuk mengatur suhu tubuhnya supaya tetap konstan, Mekanisme thermogulasi yaitu mengatur keseimbangan antara perolehan panas atau pelepasan panas. Makhluk hidup memiliki ciri-ciri tertentu, salah satunya menerima dan menaggapi rangsang.Tujuan dari praktikum termoregulasi adalah untuk mengetahui keadaan suhu tubuh pada beberapa bagian tubuh dan pada berbagai keadaan.Suhu tubuh homoiotermis (manusia). Untuk mengetahui suhu tubuh pada homoiotermis, dilakukan pengukuran suhu tubuh dengan menggunakan termometer klinis. Percobaan ini menggunakan tiga perlakuan yang berbeda yaitu posisi terbaring dengan mulut terbuka, posisi terbaring dengan mulut tertutup, setelah berkumur dengan es dan pada fossa axillaris. Percobaan ini dengan melakukan pengukuran suhu tubuh menggunakan termometer klinis yang sebelumnya telah disterilkan dengan alkohol 70%. Pengukuran suhu tubuh dilakukan sebanyak tiga kali. Tubuh berespon baik terhadap stres fisik dan stres emosional. Adanya stres menyebabkan rangsangan terhadap epinefrin dan norepinefrin sehingga kecepatan metabollisme akan meningkat yang pada akhirnya juga akan meningkatan suhu tubuh

Pada genetika manusia, apabila dijumpai suatu kasus yang dicurigai sebagai kasus pewarisan secara genetis, maka kasus tersebut dapat dipelajari dengan menelusuri silsilah dari pembawa kasus tersebut. Misalnya suatu ketika dijumpai kasus anak yang albino dalam suatu perkawinan antara ayah normal dengan ibu yang normal, maka asal-usul kelainan genetis ini dapat ditemukan dengan menelusuri silsilah keluarganya. Metode untuk menelusuri silsilah ke atas guna mendapatkan informasi genetik yang jelas disebut sebagai analisis silsilah atau pedigree analysis, sedang individu yang mula-mula dijumpai atau dicurigai memiliki kelainan genetik disebut sebagai propositus. Dengan melakukan analisis silsilah, maka kadang-kadang dapat dibuktikan apakah suatu kejadian merupakan suatu kasus pewarisan genetik ataukah sekedar kasus kebetulan saja. Kebanyakan analisis silsilah digunkan untuk mempelajari karakter yang ditentukan oleh sepasang gen. Melalui analisis silsilah maka dapat menurunkan pola penurunan suatu sifat

This study is about incidence of pork-tapeworm (Taeniasolium L.) in Purwosari village entitled "Detection of pork-tapeworm (Taeniasolium L.) infecesof people and swine in Purwosari village, Torue, sub-district of Parigi Moutong in Central Sulawesi". It was done over March and may, 2013. The goal of this research was to detect the tapeworm in feces of Purwosari village community. Observation was done based on kato-katz and direct slide methods. Stool sample were collect from 33 people, and from 33 swines. The result showed that pork-tapeworm was not detected from all sample. In addition, other worms i.e. Trichuristrichura, Ascarislumbricoides, Ancylostomaduodenale, grouped as Soil Transmited Helmin (STH), were detected from the sample. Based on these data, we recomend to the comunity to continue their hygiene in daily lifestyle.

Article Info ABSTRACT 10.30699/jambs.28.126.47 Physiological experiments show that mean blood pressure is controlled by the nervous system in long-term. The nucleus tractus solitarius (NTS), located in the dorsomedial medulla oblongata is extensively recognized as an essential brain area complicated in the integration of numerous viscerosensory processes, such as respiratory, cardiovascular, hepatic gustatory, and renal regulation mechanisms. NTS is a region of the brain stem in which primary baroreceptor afferents terminate and synapse with the rostral ventrolateral medulla (RVLM) via a nitric oxidergic pathway and hence is vital in the normal control of arterial pressure (AP). The NTS as a comparator evaluates the error signals between afferents of cardiovascular receptor and central neural structures and sends signals to nuclei that normalize the circulatory variables. Furthermore, during exercise, signals from the muscle receptors reach the NTS that activate sympathetic premotor neurons and thus cause pressor and tachycardiac responses. The GABAergic interneurons of NTS may contribute to baroreceptor reflex resetting by the inhibition of the barosensitive NTS neurons, thereby enhancing the sympathetic nerve activity. The basic functions of the NTS with respect to regulating the cardiovascular system are introduced in this review. Then, the potential mechanisms underlying cardiovascular regulation are discussed with a focus on NTS functions.

Isoniazid is a major first-line anti-tuberculosis drug indicated for the curative and preventive treatment of tuberculosis. Generally, it is administered in combination with other anti-tuberculosis drugs such as rifampicin and pyrazinamide. The hepatic metabolism of isoniazid is subject to genetic polymorphism. Several factors justify the pharmacological therapeutic monitoring of isoniazid, including inter-individual variability in pharmacokinetics, genetic polymorphism, drug interactions, compliance verification, and field factors. The administration of isoniazid may be responsible of developing dose-dependent adverse reactions in slow acetylators  patients and therapeutic failure in rapid acetylators. So determining acetylation profile at the start of treatment and adjusting the dosages are two keys pillars of optimal therapeutic management. The assays are performed on blood samples two or three hours after taking the drug. The measurements are generally performed by liquid chromatography. The purpose of this work is to detail several aspects related to the pharmacological therapeutic monitoring of isoniazid including the description of the drug, pharmacokinetic parameters and analytical conditions.

Aerobic capacity (VO2max) for any species is a key factor regarding their RBC production and the associated hemoglobin that is carried within the red blood cells. Hemoglobin (Hb) is vital for oxygen transport, in which animals oriented towards athletically-inclined nature will need more oxygen to fulfill their physiological functions, therefore needing more hemoglobin, and more erythrocytes (RBCs) to draw from. Within this study, there was an essential comparison between species that are highly active, with high aerobic capacity and those that were sedentary, or moved very little in comparison, with low aerobic capacity. The study had hypothesized that species that were of low aerobic capacity would have lower RBC counts and lower hemoglobin determinations, while those that were of higher aerobic capacity would have higher RBC counts. The study had predicted the horse and dog species would have the highest counts within the respective parameters of the study, while the sheep and bovine species would have the lowest counts. These postulations ended up being for the most part true, besides for a few of the test where the bovine remained an outlier. The literature and recent studies that are of similar nature have concluded very analogous results within their findings, suggesting that this study was properly approached and executed.

The bioactivity of the extractable organic matter (EOM) of particulate matter (PM) exhausted from major urban combustion sources, including residential heating installations (wood-burning fireplace and oil-fired boiler) and vehicular exhaust from gasoline and diesel cars), was investigated in vitro by employing multiple complementary cellular and bacterial assays. Cytotoxic responses were investigated by applying the MTT ((3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)) bioassay and the lactate dehydrogenase (LDH) release bioassay on human lung cells (MRC-5). Sister Chromatids Exchange (SCE) genotoxicity was measured on human peripheral lymphocytes. Lipid peroxidation potential via reactive oxygen species (ROS) was evaluated on E. coli bacterial cells by measuring the malondialdehyde (MDA) end product. Furthermore, the DNA damage induced by the organic PM fractions was evaluated by the reporter (b-galactosidase) gene expression assay in the bacterial cells, and, by examining the fragmentation of chromosomal DNA on agarose gel electrophoresis. The correlations between the source PM-induced biological endpoints and the PM content in polycyclic aromatic hydrocarbons (PAHs), as typical molecular markers of combustion, were investigated. Fireplace wood smoke particles exhibited by far the highest content in total and carcinogenic PAHs followed by oil boilers, diesel and gasoline emissions. However, in all bioassays, the total EOM-induced toxicity, normalized to PM mass, was highest for diesel cars equipped with Diesel Particle Filter (DPF). No correlation between the toxicological endpoints and the PAHs content was observed suggesting that cytotoxicity and genotoxicity are probably driven by other extractable organic compounds than the commonly measured unsubstituted PAHs. Clearly, further research is needed to elucidate the role of PAHs in the biological effects induced by both, combustion emissions, and ambient air particles.

Background Ultrasound elasticity imaging provides biomechanical and elastic properties of vascular tissue, with the potential to distinguish between tissue motion and tissue strain. To validate the ability of ultrasound elasticity imaging to predict structurally defined physical changes in tissue, strain measurement patterns during angioplasty in four bovine carotid artery pathology samples were compared to the measured physical characteristics of the tissue specimens. Methods Using computational image-processing techniques, the circumferences of each bovine artery specimen were obtained from ultrasound and pathologic data. Results Ultrasound-strain-based and pathology-based arterial circumference measurements were correlated with an R2 value of 0.94 (p = 0.03). The experimental elasticity imaging results confirmed the onset of deformation of an angioplasty procedure by indicating a consistent inflection point where vessel fibers were fully unfolded and vessel wall strain initiated. Conclusion These results validate the ability of ultrasound elasticity imaging to measure localized mechanical changes in vascular tissue.

Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

Hemoglobin (Hb) solution-based blood substitutes are being developped as oxygen^carrying agents for the prevention of ischemic tissue damage and low blood volume-shock. However, the cell-free Hb molecule has intrinsic toxicity to the tissue since harmful reactive oxygen species (ROS) are readily produced during auto-oxidation of Hb from the ferrous state to the ferric state, and the cell-free Hb also causes distortion in the oxidant/antioxidant balance in the tissues. There may be further hidden dangers in the use of free Hb as a blood substitute. It has been reported that Hb has peroxidase-like catalytic activity oxidizing peroxidase substrates such as aromatic amines. Here, we observed the Hb-catalyzed ROS production coupled to oxidation of a neurotransmitter precursor, beta-phenylethylamine (PEA). Addition of PEA to Hb solution resulted in generation of superoxide anion (O2*-). We also observed that PEA increases the Hb-catalyzed monovalent oxidation of ascorbate to ascorbate free radicals (Asc*). The O2*- generation and Asc* formation were detected by O2*--specific chemiluminescence of the Cypridina liciferin analog (CLA) and electron spin resonance spectroscopy (ESR), respectively.  PEA-dependent O2*- production and  monovalent oxidation of ascorbate in the Hb solution occuered without addition of H2O2, but a trace of H2O2 added to the system greatly increased the production of both O2*- and Asc*. Addition of glutathione (GSH) completely inhibited the PEA-dependent production of  O2*- and Asc* in Hb solution. We propose that the  O2*- generation and Asc* formation in the Hb solution are due to the pseudo-peroxidase activity-dependent oxidation of PEA and resultant ROS may damage the tissues rich in monoamines, if the Hb-based blood substitutes were circulated without addition of ROS scavengers such as thiols.

Background: Regular," moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect). These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such ...

Background Ultrasound elasticity imaging provides biomechanical and elastic properties of vascular tissue, with the potential to distinguish between tissue motion and tissue strain. To validate the ability of ultrasound elasticity imaging to predict structurally defined physical changes in tissue, strain measurement patterns during angioplasty in four bovine carotid artery pathology samples were compared to the measured physical characteristics of the tissue specimens. Methods Using computational image-processing techniques, the circumferences of each bovine artery specimen were obtained from ultrasound and pathologic data. Results Ultrasound-strain-based and pathology-based arterial circumference measurements were correlated with an R2 value of 0.94 (p = 0.03). The experimental elasticity imaging results confirmed the onset of deformation of an angioplasty procedure by indicating a consistent inflection point where vessel fibers were fully unfolded and vessel wall strain initiated....

The bioactivity of the extractable organic matter (EOM) of particulate matter (PM) exhausted from major urban combustion sources, including residential heating installations (wood-burning fireplace and oil-fired boiler) and vehicular exhaust from gasoline and diesel cars), was investigated in vitro by employing multiple complementary cellular and bacterial assays. Cytotoxic responses were investigated by applying the MTT ((3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)) bioassay and the lactate dehydrogenase (LDH) release bioassay on human lung cells (MRC-5). Sister Chromatids Exchange (SCE) genotoxicity was measured on human peripheral lymphocytes. Lipid peroxidation potential via reactive oxygen species (ROS) was evaluated on E. coli bacterial cells by measuring the malondialdehyde (MDA) end product. Furthermore, the DNA damage induced by the organic PM fractions was evaluated by the reporter (β-galactosidase) gene expression assay in the bacterial cells, and, by examining the fragmentation of chromosomal DNA on agarose gel electrophoresis. The correlations between the source PM-induced biological endpoints and the PM content in polycyclic aromatic hydrocarbons (PAHs), as typical molecular markers of combustion, were investigated. Fireplace wood smoke particles exhibited by far the highest content in total and carcinogenic PAHs followed by oil boilers, diesel and gasoline emissions. However, in all bioassays, the total EOM-induced toxicity, normalized to PM mass, was highest for diesel cars equipped with Diesel Particle Filter (DPF). No correlation between the toxicological endpoints and the PAHs content was observed suggesting that cytotoxicity and genotoxicity are probably driven by other extractable organic compounds than the commonly measured unsubstituted PAHs. Clearly, further research is needed to elucidate the role of PAHs in the biological effects induced by both, combustion emissions, and ambient air particles.

The use of immunofluorescence with affinity-purified antibodies enabled cytological localization of nerve growth factor-like material in the rat. Immunoreactivity was observed along various nerve tracts of the foetal rat brain and spinal cord at day 15 of gestation. Longitudinal pathways in ventral and dorsal spinal cord, ventral lower brain stem, posterior commissure, retroflex fascicle and in the olfactory bulb were all positive. A weaker and more widely spread immunostaining was visible in many areas in the central nervous system. Cranial nerves were strongly immunoreactive. Neuronal perikarya in the retina and the olfactory mucosa as well as filae olfactoriae and the olfactory nerve all the way to the olfactory bulb were also positive. In sensory ganglia and peripheral nerves most immunoreactivity was confined to supporting tissues, probably including Schwann cells. In irides, the pattern of immunoreactivity was similar to that of the sensory and autonomic innervation. More inte...

Sixteen hour polygraphic recordings (EEG, EOG and EMG) were obtained from 14 adult cats after intraperitoneal injections of propranolol (5 mg/kg) or pindolol (0.1 or 0.5 mg/kg). All injections moderately increased waking, which consisted mainly of a sedated drowsy stage. Both drugs also decreased deep slow wave sleep, while light slow wave sleep remained at control levels. The changes were more marked after propranolol, which also significantly reduced paradoxical sleep (PS). The decrease in the deeper stages of sleep and PS is suggested as being due to blockade of the central adrenergic beta-receptors per se and/or antagonistic effects of the beta-blockers on 5-HT receptors. The results agree with the finding that beta-blockers cause insomnia in susceptible patients, but they do not suggest that intensified dreaming or nightmares reported by others are likely to be caused by increased PS.

Article Info ABSTRACT 10.30699/jambs.29.132.46 Background & Objective: Pathophysiology of Ischemia/Reperfusion (Isc/R) can cause renal and hepatic damages. Naringenin (NAR) is a flavonoid with potent antioxidant properties. In the present study, the effects of NAR on the liver after the renal Isc/R procedure were investigated. Materials & Methods: Sixty-four Wistar rats were divided into eight groups. The animals in the control group received dimethyl sulfoxide (DMSO). Group 2 as the Isc/R group went under the Isc/R procedure. Groups 3, 4, and 5 as the NAR groups received 20, 50, and 100 mg/kg of NAR, respectively. Groups 6, 7, and 8 were the Isc/R+NAR groups. The NAR was administrated for four consecutive weeks orally. Levels of the expression of p53, Bcl2, and Bax genes were assessed. The histomorphometric features, Total Antioxidant Capacity (TAC), nitric oxide (NO), inflammatory cytokines, and hepatic enzymes were analyzed. Results: We observed that Isc/R increased inflammatory cytokines, NO level, histomorphometric parameters, the expression of p53 and Bax genes, and enzymes, compared to the control group (P<0.05). On the other hand, the latter intervention decreased TAC and Bcl2 gene expression significantly (P<0.05), in comparison with the control group. All values significantly (P<0.05) diminished in the NAR and NAR+Isc/R groups, compared to the Isc/R group. However, the TAC level and Bcl2 were higher in the NAR and NAR+Isc/R groups than the Isc/R group. Conclusion: The NAR could recover the liver damage resulting from Isc/R. This impact could be attributed to the antioxidant effects.

Article Info ABSTRACT 10.30699/jambs.28.129.175 Background & Objective: Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes mellitus (T2DM) and the leading cause of vision loss in working-age adults. Vitamin A (retinol) has a role in the mechanism of vision process and retinol binding protein-4 (RBP4), is a carrier of vitamin A, and as an adipokine may be associated with increased risk for insulin resistance and DR. This case-control study was aimed to determine and analyze plasma RBP4-to-vitamin A ratio in relation with terms of DR severity. Materials & Methods: In the present analytical cross-sectional study, 51 T2DM patients, aged 48-73 years old, were enrolled from those attending to the Ophthalmology Center of Vali-e Asr Hospital, Zanjan, Iran. Patients were categorized as non-retinopathy diabetic patients (NRDP) without any eye problem, those with mild non-proliferative DR (mild NPDR) (n=12), those with severe non-proliferative diabetic retinopathy (severe NPDR) (n=12), and those with proliferative DR (PDR) (n=12); a control group (n=15) was also considered. Anthropometric parameters, BMI, and WHR were determined and blood sample were taken from each participant after overnight fasting (12-14h) to measure their biochemical parameters. Serum RBP4 and vitamin A levels were measured via ELISA and C18 reverse-phase HPLC methods, respectively. Results: Plasma RBP4 concentration was significantly higher in three different stages of DR than that of the control group suffering from diabetes (77.0±11.0, 81.7±10.9 and 88.3±11.9 vs. 71.4±12.3, respectively; P=0.004). The ratio of plasma RBP4-to-retinol in DR groups was found to be significantly higher than that in the control group suffering from diabetes (0.21±0.06, 0.27±0.12 and 0.28±0.07 vs. 0.16±0.14, respectively; P=0.001). Conclusion: Higher plasma RBP4-to-vitamin A ratio was related to DR severity. Further experimental studies with larger scales are recommended.

This study provides a confirmation of the need to adopt the HACCP method (Hazard Analysis Critical Control Point) in slaughterhouses as a tool to eradicate the Human Brucellosis. Indeed this assessment made in our study is an indirect indicator for the presence of the disease in a country on one hand, but also about the transmission risk of the disease from animals to humans in a professional context at high risk, and secondarily to the general population by food consumption. Slaughterhouses are the most propitious places for the transmission of this disease to humans and also the point spread of this zoonosis seen as a biological danger to the population. The general objective of this study made at the Slaughterhouse of the Bertoua city (East Region of Cameroon) was to evaluate the errors related to the professional activity of slaughterhouse workers with regard of the Human Brucellosis, in a context where the application of the HACCP method is not respected. Its specific objectives were to detect the presence of the Human brucellosis in that slaughterhouse, to determine its prevalence among slaughterhouse workers and to make them more aware about the existence of this zoonosis. We included in our study, all slaughterhouse workers from the city of Bertoua, who signed the informed consent form for the participation in the study, and also the absent staff due to illness. We excluded from our study any slaughterhouse workers absent at the time of data collection and reported to be in good health by their colleagues. At the end of this study, we found a prevalence of 31.4% for human brucellosis cases due to a bad slaughtering system which did not comply with the safety and hygiene measures in force. Professional exposure was related to the failure to use individual protection equipments (boots, aprons, goggles, bibs, gloves and helmet) and collective protection equipments (disinfectants/antiseptic and slaughterhouse toilets). The Biological signs related to the Human Brucellosis found among sick slaughterhouse workers hospitalized in different health care structures from the city were: neutropenia associated with an increase of ESR, CRP and transaminases. The most frequent symptoms noticed among them were: asthenia, fever, generalized pain and headache.

Keywords: Human Brucellosis, Slaughterhouse, Slaughterhouse Workers, Rose Bengal Test, Prevalence, East Cameroon

Previously, generation of superoxide anion (O2 •-) catalyzed by Cu-binding peptides derived from human prion protein (model sequence for helical Cu-binding motif VNITKQHTVTTTT was most active) in the presence of catecholamines and related aromatic monoamines such as phenylethylamine and tyramine, has been reported [Kawano, T., Int J Biol Sci 2007; 3: 57-63]. The peptide sequence (corresponding to helix 2) tested here is known as threonine-rich neurotoxic peptide. In the present article, the redox behaviors of aromatic monoamines, 20 amino acids and prion-derived tyrosine-rich peptide sequences were compared as putative targets of the oxidative reactions mediated with the threonine-rich prion-peptide. For detection of O2 •-, an O2 •-specific chemiluminescence probe, Cypridina luciferin analog was used. We found that an aromatic amino acid, tyrosine (structurally similar to tyramine) behaves as one of the best substrates for the O2 •-generating reaction (conversion from hydrogen peroxide) catalyzed by Cu-bound prion helical peptide. Data suggested that phenolic moiety is required to be an active substrate while the presence of neither carboxyl group nor amino group was necessarily required. In addition to the action of free tyrosine, effect of two tyrosine-rich peptide sequences YYR and DYEDRYYRENMHR found in human prion corresponding to the tyrosine-rich region was tested as putative sub-strates for the threonine-rich neurotoxic peptide. YYR motif (found twice in the Y-rich region) showed 2-to 3-fold higher activity compared to free tyrosine. Comparison of Y-rich sequence consisted of 13 amino acids and its Y-to-F substitution mutant sequence revealed that the tyrosine-residues on Y-rich peptide derived from prion may contribute to the higher production of O2 •-. These data suggest that the tyrosine residues on prion molecules could be additional targets of the prion-mediated reactions through intra-or inter-molecular interactions. Lastly, possible mechanism of O2 •-generation and the impacts of such self-redox events on the conformational changes in prion are discussed.

Objectives: Studies have proposed two opposing roles for copper-bound forms of prion protein (PrP) as an anti-oxidant supporting the neuronal functions and as a pro-oxidant leading to neurodegenerative process involving the generation of reactive oxygen species. The aim of this study is to test the hypothesis in which putative copper-binding peptides derived from PrP function as possible catalysts for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro. Materials and methods: Four peptides corresponding to the copper (II)-binding motifs in PrP were synthesized and used for analysis of peptide-catalyzed generation of superoxide in the presence of Cu (II) and other factors naturally present in the neuronal tissues. Results: Among the Cu-binding peptides tested, the amino acid sequence corresponding to the Cu-binding site in the helical region was shown to be the most active for superoxide generation in the presence of Cu(II), hydrogen peroxide and aromatic monoamines, known precursors or intermediates of neurotransmitters. Among monoamines tested, three compounds namely phenylethylamine, tyramine and benzylamine were shown to be good substrates for superoxide-generating reactions by the Cu-bound helical peptide. Conclusions: Possible roles for these reactions in development of prion disease were suggested.