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Tyrosinase is a copper-containing monooxygenase involved in thecatalysis of the hydroxylation and oxidation reaction of monophenols and diphenols, respectively, into O-quinones intermediates. Tyrosinase is mainly involved in melanogenesis via two reactions. Firstly, 3,4-dihydroxyphenylalanine is produced through tyrosine hydroxylation the nit oxidized into dopaquinone, and finally gives melanin. However, dopaquinones can results in neuronal damage and cell death through the excessive production, suggesting that tyrosinase may be implanted in the formation human brain’s neuromelanin and association with Parkinson’s diseases. Thus, down regulating the melanin pigments and its intermediates by inhibiting tyrosinase activity is the major pharmaceutical challenge to prevent hyperpigmentation, in addition to therapy of neuromelanin disorders. Thus, this review has been focused on exploring the biochemical and molecular properties of tyrosinase from different sources and its potential inhibition with different natural and synthetic compounds.

Paleozoic Zeitoun, Desouqy and Dhiffah formations represent source rocks to hydrocarbon in Faghur basin, north Western Desert, Egypt. They are characterized by a sufficient amount of organic matter belonging to kerogen type III and mixed type II/III, which are in maturation stage. A 1D-basin modeling was performed by using geological and geochemical data of the Paleozoic source rocks from five wells in Faghur basin, north Western Desert, Egypt. These data used in 1D basin modeling for constructing and understanding of burial and thermal geo-histories of Faghur basin and for simulating and predicting the timing of petroleum and expulsion for the Paleozoic source rocks in the studied wells. Burial and thermal history models indicate that the Zeitoun Formation entered onset of oil generation in the studied wells during Late Cretaceous (100.10–91.65 my) with transformation ratio (TR) 10–25, peak oil during Late Cretaceous (91.65–79.30 my) with TR 25–50 and late oil stage at Late Cretaceous (79.30 my-0) to present day with TR 50–60.45. Desouqy Formation entered onset of oil generation also during Late Cretaceous (94.43–73.60 my) with TR 10–25 in the studied wells, peak oil during Late cretaceous (73.60–62.40 my) with TR 25–50 and Late oil stage during Late Cretaceous to present day (62.40 my-0) with TR 50–61.82. Dhiffah Formation entered onset of oil generation in the studied wells during Early to Late Cretaceous (102.11–92.27 my) with TR 10–25, peak oil during Late Cretaceous (92.27–86.40 my) with TR 25–50 and late oil stage at Late Cretaceous to present day (86.40 my-0) with TR 50–67.27. No cracking oil to gas in the studied Paleozoic source rocks in the studied wells. These basin modeling results also suggest that the Paleozoic source rocks act as an effective source rock where a significant amount of petroleum is expected to be generated and expelled to any nearby prospect reservoir rocks in the Faghur basin. Keywords: Faghur basin, Paleozoic source rocks, 1D basin modeling, Transformation ratio (TR), Hydrocarbon generation and expulsion

CYTOSINE Deaminase (CDA) is a non-human enzyme converting cytosine to uracil, with significant implementation on various cancer therapeutic approaches especially prodrug mediated therapy using 5-fluorocytosine into 5-fluorouracil. However, the lower catalytic/ thermal stability and higher antigenicity of this enzyme are the main challenges for further its clinical applications, thus, screening for thermostable enzyme with higher turnover activity was the objective of this study. Among the recovered thermotolerant fungal isolates, Aspergillus fumigatus has been selected as potent CDA producer. Upon nitrogen starvation, the yield of intracellular CDA by A. fumigatus was significantly increased by about 5 folds, comparing to control. The enzyme was purified from thermotolerant A. fumigates into its electrophoretic homogeneity by ion-exchange and gel-filtration chromatography by 4.4 purification folds and 29.9% yield, respectively, with molecular subunit structure 48 kDa under denaturing-PAGE. The purified enzyme showed an optimum pH 7.0, optimum reaction temperature 37°C. The maximum affinity (Km) and reaction velocity (Vmax) of purified CDA was 0.08 mM and 400 μmol/min/mg on cytosine as substrate. At 37°C, the half-life time (T1/2) of purified CDA was about 8 h, ensuring the structural/ catalytic thermal stability of this enzyme. Based on these preliminary results, A. fumigatus CDA could be a scaffold for further in vivo studies on cancer prodrug-mediated therapies, or gene therapy applications.

Duwi Formation shale deposits at Safaga – Quseir area were assessed by rock eval pyrolysis for its shale oil potentiality. The studied shale’s organic matter are mainly of type I, type II, mixed type I/II in addition to some of type III. The studied shale is described as very good source rock with total organic carbon (TOC > 2 wt%). The kerogen maturation in the studied samples is immature according to PI and Tmax. Extracted shale oil from the studied samples as bitumen was fractionated by liquid chromatography (LG) into saturated hydrocarbon, aromatic hydrocarbon, resin and asphaltene. The saturated hydrocarbon was described by gas chromatography (GC), the pristane/phytane, isoprenoids/n-alkane and CPI ratios show that, samples were deposited in marine environment with some input of terrestrial environment and are characterized by immature level.The X-Ray Diffraction (XRD) analysis for the studied shale samples show their bulk minerals are mainly quartz, calcite, dolomite, gypsum, hematite and pyrite in addition to apatite and fluorapatite. While their clay minerals are mainly smectite and kaolinite. The chemical composition of the studied samples showed high concentration of trace elements such as Co, Cr, Cu, Ni, V and Zn which in turn through more lights on the depositional environment of the organic matter. Keywords: Safaga, Quseir, Duwi Formation, Oil shale, Rock-Eval pyrolysis, Gas chromatography

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.

The Lower Miocene Nukhul Formation was deposited during early stages of Gulf of Suez rifting. Outcrop of this formation at Gebel el Zeit, Egypt is up to 100 m (328 ft) in thickness and consists of lower sandstone-dominated and upper carbonate-dominated units. Samples were collected from the Nukhul Formation outcrop in order to describe the lithofacies, mineralogy, and petrographic characteristics to better understand the hydrocarbon reservoir potential of the unit. The investigations showed that the lower part of Nukhul Formation at North Gebel el Zeit consists of poorly sorted, dolomitic sandstone and sandy dolomite which were deposited in a shallow-marine setting. The presence of polycrystalline and crushed quartz grains in Nukhul strata indicates that these strata were sourced by recycled sediments associated with local uplift tied to rifting. The upper Nukhul consists of dolomitized carbonates with preservation of original textures; primary limestone depositional textures include intraclast packstone, rudstone, and coral-algal boundstone, wackestone, and grainstone with minor floatstone. Carbonate rock strata were deposited in shallow marine, peritidal to subtidal environments that developed on fault-block highs. The presence of zoned saddle dolomite suggests some component of fault-controlled fluid flow. Reservoir characteristics of the Lower Miocene Nukhul Formation at the Gebel el Zeit indicates favorable properties for reservoir development in both the lower siliciclastic-dominated dolomite and the upper dolomitized carbonate portions of the formation.

Within Alam El Bueib Formation (AEB), thin sandstone beds of approximately 15.24 m (~50 ft) total thickness, are considered to be the main conventional hydrocarbon-producing zone in the Western Desert. However, the shale intervals within the AEB can be an unconventional reservoir target. In this study, we focus on evaluating these shale units through geochemical analysis, to determine the total carbon, total sulfur, total organic carbon (TOC), and Rock–Eval pyrolysis. TOC is an essential property needed to determine the productive shale gas play. Total organic carbon combined with other geochemical data is important in evaluating the potential of shale gas reservoirs as it is related to the amount of kerogen, the produced hydrocarbon content. The TOC in the studied samples indicates poor to very good organic continent, while the hydrocarbon potentiality (S1 and S2) indicates poor source potential. The hydrogen index reflected kerogen type III/II. These data indicate that AEB Formation may be considered as a good source for generating hydrocarbons (mainly gas with minor amount of oil). The maturation evaluated by using “Tmax” indicates immature to marginally mature source rock, and production index ‘‘PI” represents oil and gas production in case of maturation.

The Paleozoic rocks in North Africa are prolific with source rocks that contribute petroleum to giant fields especially in Algeria and Libya. The coeval subsurface source rocks from the Devonian and Carboniferous in the Western Desert of Egypt have been evaluated in the present study. The rocks from Zeitoun, Desouqy, and Dhiffah formations have been evaluated based on integration of the palynofacies, organic geochemical analysis, and well logging. The study depends on samples from five wells that are Buchis-1X, Phiops-1X, Siwa-D-1X, Tayim West-1X, and WKAL C-1XST. The distribution of palynofacies categories are statistically investigated by the principal component analysis (PCA) that specified the proximal-distal environmental trends by the values of component 1 that attributed to the terrestrial organic sources. The analyses revealed mostly poor, fair to good organic enrichments and poor to fair source potential in the studied rocks. The samples are mostly thermally mature, uncontaminated, and of gas prone type III and mixed oil/gas prone type II/III kerogen. The geological conditions that lead to the large difference in the hydrocarbon source potentiality between western North Africa and source rocks evaluated in this study from Egypt have been discussed. It is suggested that these differences resulted from the larger thickness of Paleozoic rocks and the increase in burial depths of the depocenters in the western side that lead to higher maturity levels that are responsible for the organic conversions and hydrocarbon expulsion.

Pacemaker is a vital electronic medical device that manages the abnormal heart rhythm. One of the technical problems that pacemaker suffers from is its power source which is a lithium-ion battery with short life compared to patient life. So, this work is concerned with designing and simulation of a novel way to harvest energy from pulsatile pressure inside superior vena cava (SVC) to recharge pacemaker battery. The working principle depends on covering the pacemaker lead (which is a wire inserted through SVC during pacemaker implantation surgery) with a layer of polydimethylsiloxane (PDMS) and creates some cavities in this layer. These cavities would be covered with a thin diaphragm of PDMS which will be in contact with pulsatile blood pressure inside SVC. Under this diaphragm, there will be a lead zirconate titanate (PZT) layer with an area of 2.5 × 6 mm2 and thickness of 0.028 mm working as a cantilever that is fixed in cavity wall from one side and free from other side. When the pressure varies inside SVC in a harmonic manner, the PDMS diaphragm deflects up and down causing the PZT layer to deform and hence generate pulsations of electricity for each heartbeat. The harvesting process was simulated and showed that power of 52 nW could be harvested for each cavity which could be used to recharge the pacemaker battery and avoid replacing it.

The Nubian Sandstone is a thick sequence of clastic and thin carbonate sediments in the Jebel El Zeit section of eastern Egypt. The sequence is composed mainly of sandstone with shale and minor carbonate interbeds and was deposited in continental and fluviomarine to marine settings. Petrographically, quartz arenite and quartz wacke are the main facies of Nubian Sandstone. They have different secondary components, cement and matrix types, reflecting their different depositional environments and diagenetic histories. The Nubian Sandstone is one of the most prolific hydrocarbon reservoirs in the Gulf of Suez oil province.The Nubian Sandstone has good reservoir quality with porosity varying from 10% to 29%, and permeability of up to 5000 millidarcies. The quality of the reservoir depends on its proportions of shale, diagenetic history and the depth of burial (compaction). X-ray diffraction and scanning electron microscope analyses indicate that kaolinite is the main clay mineral and is derived from the altera...

The selection of drilling fluid is considering main factor for oil and natural gas well drilling processes success. Drilling fluids play important role in carrying and suspending drilling cuttings, high rates of penetration, maximizing bit life, minimizing fluid loss into the formation and stability of the formation. In this study, clays collected from claystone quarries in Gabal Hamza – um Qumar north Cairo-Ismailia Desert Road, Egypt for its application as water base drilling mud. These clays consist mainly of montmorillonite in addition to kaolinite as indicated by X-ray diffraction (XRD) and scanning electron microscope (SEM). The rheological and filtration properties of drilling fluids were designed with different types of additives such as Caustic soda, CarboxiMethyl Cellulose (CMC) and polyanionic cellulose polymer (PACR). Although designed different types of polymer compositions did not meet the required rheological and filtrate properties; the addition of Caustic soda, CarboxiMethyl Cellulose (CMC) and polyanionic cellulose polymer (PACR) gave better rheological and filtrate properties of bentonite suitable for drilling medium depth wells.

Introduction: Possible approaches for postoperative analgesia after pediatric inguinoscrotal surgery are caudal block by bupivacaine/ketamine (BK) and bupivacaine/magnesium sulfate (BM). Aim: The purpose of the following study is to compare the analgesic efficacy and safety of ketamine and magnesium sulfate in combination with bupivacaine for caudal blockade in pediatric patients after inguinoscrotal operations. Materials and Methods: Patients randomly received one of the two solutions for caudal epidural injection after induction of general anesthesia. Group-BK: Were given a mixture of 0.25% bupivacaine and 0.5 mg/kg of ketamine. Group-BM: Were given a mixture of 0.25% bupivacaine and 50 mg magnesium sulfate. Postoperatively, a blinded post-anesthesia care unit nurse assessed the quality of analgesia with a visual pain analog scale (VPAS). Significant pain is defined as one that has a VAPS of ≥3. Results: Forty American Society of Anesthesiologists I-II children (20 in each group) completed the study. The two groups were comparable regards age, sex, body mass index, anesthesia and surgery durations, recovery time and sevoflurane concentration. The mean duration of caudal analgesia ± standard deviation was 462 ± 17.2 min versus 398.05 ± 12.9 min for BK and BM groups, receptively (P < 0.001). Supplemental rectal paracetamol within 12 h postoperatively were 15% for BK group versus 25% for BM (P = 0.05). Four patients in BK group only experienced postoperative nausea and vomiting (P = 0.053). Conclusion: Caudal administration of BK is efficient and safe for pediatric inguinoscrotal operations with longer postoperative analgesia than BM sulfate.

Eight shale samples related to the Duwi Formation (Campanian-Maastrichtian) of the Abu Tartur mines of the southwestern desert of Egypt were petrographically, mineralogically, and geochemically studied. The study results indicate that the detrital material of these shales were derived mainly from mafic to ultramafic components of the basement rocks under intensive chemical weathering and deposited in an alkaline reducing marine environment of low energy and these shales do not attain the requirements of hydrocarbon production.

Organophilic kaolinitic black shale was prepared through incorporation of cetyl trimethyl ammonium bromide (CTAB C16) as surfactant with natural kaolinitic black shale. It was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. The acrylic acid modifying agent can be utilized to improve the distribution of the organophilic kaolinitic black shale in the rubber matrix. The ethylene propylene diene monomer was mixed with different concentrations of modified organophilic kaolinitic black shale. The dispersion of the modified organophilic kaolinitic black shale was characterized by scanning electron microscopy and X-ray diffraction, which confirmed the formation of exfoliated nanocomposites at lower clay content. The elastomeric compound was filled with kaolinitic black shale and then it was analyzed by undergoing the physicomechanical properties and thermal gravimetric analysis. The nanocomposites showed remarkable improvements in tensile strength, elongation at break, Young’s modulus, and hardness. In addition, increase in thermal stability due to the presence of modified organophilic kaolinitic black shale was observed.

Nano-sized silica gels have been synthesized by the refluxing of white sandstone with 2 M NaOH and subsequently undergoing gelation process using 1 M citric acid. The properties of the synthesized materials were studied using TGA, XRD, nitrogen adsorption and desorption analysis, FTIR, and HRTEM. The features of the prepared silica gels have been found to be dependent on: (1) type of silica precursor, (2) presence of microwave irradiation, (3) time of aging process under microwave irradiation. The adsorption of barium, strontium, magnesium and calcium ions by various silica gels synthesized via the sol–gel route was comparatively studied. In general, silica gel nanoparticles that were prepared under microwave irradiation for sodium silicate (sandstone precursor) showed high adsorption activity in comparison to silica gel sample prepared via conventional aging conditions. The affinity of cations for the silica gel nanoparticles was magnesium ≫ calcium ≫ barium > strontium.

Tomato is one of the world's major vegetable crops. Like other important crops, tomatoes also suffer huge crop losses due to many diseases. Among these diseases, late blight caused by Phytophthora infestans. The present study was conducted to induce defence reaction in tomato plants against late blight disease under field conditions using some abiotic agents. Tomato plants sprayed by ethyl salicylic acid (2.5 ml/20 litre water) resulted in lowering disease incidence to great extent( from 25±1.41% in control plants to 1.66±1.03%), followed by coconut milk solution (1%) and Agrispon® (1%). These three agents were found to induce accumulation of sesquiterpenoid stress metabolites (phytoalexins) in tomato fruits when they were tested for its elicitation capability. Rishitin, lubimin, phytoberin and unknown compound were detected in tomato fruit diffusates treated by abiotic agents. This is the first record that these agents elicit phytoalexins in tomato fruits.

In this study, Egyptian shales from Wadi El Natrun were tested for their potential and possibility to meet the required drilling mud properties. Activation of these shales was performed using the most popular (Na2CO3), carboxy-methylcellulose, and polymers. The drilling mud qualities of the shales from Wadi El Natrun were significantly improved with additives and upgraded to have rheological properties compatible with American Petroleum Institute and Oil Companies Material Association specification.

The Late Eocene rocks near Gabal Libni, northern Sinai consists mainly of claystone. The mineralogical and the geochemical analyses indicate that this shale consists mainly of montmorillonite of homogenious major elements. This shale may be used in the economic application of the sodium bentonite.

In this study, the possible role of oxidative stress and nitric oxide (NO) synthase isoforms in the development of morphine tolerance and dependence, and effect of alpha-lipoic acid on these parameters were investigated in mice. The development of morphine tolerance as measured by the hot plate test and dependence, as assessed by naloxone-precipitated withdrawal manifestations, produced an increase in brain glutamate and malondialdehyde (MDA) levels and NO production as well as a decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity. Also, the development of these syndromes increased inducible but not neuronal NO synthase mRNA and protein expressions in mice brain. Co-administration of alpha-lipoic acid (α-LA) inhibited the development of morphine tolerance and dependence, their associated biochemical alterations, except elevation of brain glutamate level, and their associated increase in brain inducible NO synthase mRNA and protein expressions. The inhibitory effect of α-LA on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the selective inducible NO synthase inhibitor, aminoguanidine. On the other hand, this inhibitory effect of α-LA was not changed by concurrent administration of the selective neuronal NO synthase inhibitor, 7-nitroindazole but antagonized by concurrent administration of the NO precursor, L-arginine. These results suggest that α-LA through inhibition of morphine-induced oxidative stress and increase in the expression and activity of inducible NO synthase in the brain can attenuate the development of morphine tolerance and dependence.

In this study, the effect of thymoquinone on morphine-induced tolerance and dependence in mice was investigated. Repeated administration of thymoquinone along with morphine attenuated the development of morphine tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone-precipitated withdrawal manifestations. Concurrently, morphine-induced progressive increase in brain malondialdehyde (MDA) level and nitric oxide (NO) production as well as progressive decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity were inhibited by co-administration of thymoquinone. Morphine-induced progressive increase in brain glutamate level was not inhibited by concomitant administration of thymoquinone. Similarly, co-administration of thymoquinone inhibited naloxone-induced increase in brain MDA level, NO overproduction and decrease in brain intracellular GSH level and GSH-Px activities but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The inhibitory effect of thymoquinone on morphine-induced tolerance and dependence on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the NO synthase inhibitor, L -N (G)-nitroarginine methyl ester. On the other hand, this inhibitory effect of thymoquinone was antagonized by concurrent i.p. administration of NO precursor, l -arginine. In addition, concomitant administration of thymoquinone inhibited morphine tolerance and dependence-induced increase in inducible but not in neuronal NO synthase mRNA expression in mice brain. These results demonstrate that inhibition of morphine-induced oxidative stress, increase in the expression of brain inducible NO synthase and NO overproduction by thymoquinone can attenuate the development of morphine tolerance and dependence.

The analgesic effect of acute i.p. administration of amitriptyline (norepinepherine and serotonin reuptake inhibitor), clomipramine (serotonin reuptake inhibitor) and desipramine (norepinepherine reuptake inhibitor) was studied in chronic constriction injury (CCI) model of sciatic nerve in rats and mRNA and protein expression of inducible nitric oxide synthase (iNOS) were also investigated. Acute treatment with amitriptyline and clomipramine produced antinociceptive effects after sciatic nerve injury and blockade of norepinephrine reuptake using desipramine did not demonstrate antinociceptive effects. The antinociceptive effect of amitriptyline, not clomipramine, was augmented by the selective iNOS inhibitor, aminoguanidine. Amitriptyline inhibited iNOS mRNA and protein expression in cerebellum and hippocampus. However, desipramine altered neither iNOS expression at mRNA level nor at post-transcriptional level. Based on our experimental findings, we conclude that the analgesic effect of the dual norepinepherine and serotonin reuptake inhibitor, amitriptyline, is partially due to inhibition of central iNOS.

Background Postoperative emergence agitation (EA) is still a problem in sevoflurane-based anesthesia in children. Among the solutions of this problem is giving caudal anesthesia during operations in the lower half of the body. The aim of this study was to evaluate the addition of magnesium sulfate to bupivacaine in caudal block for the prevention of EA. Materials and methods In this prospective, randomized, double-blind study, 80 children aged 1-6 years, ASA I, undergoing unilateral hernia repair/orchiopexy with sevoflurane-based anesthesia were allocated into one of two groups: either bupivacaine 1 ml/kg 0.25% plus magnesium 50 mg (BM group) or bupivacaine 1 ml/kg 0.25% (B group) received in caudal block. EA was evaluated in both groups using the Pediatric Anesthesia Emergence Delirium scale and Aono's scale. The sedation score, the recovery time, and the occurrence of complications were assessed during the stay in the postanesthesia care unit. Results Only 72 children completed the study (36 in each group). There was a statistically significant difference in the Pediatric Anesthesia Emergence Delirium scale, the value being lower in the BM group than in the B group at 5 min [6 (5-17) compared with 8 (5-18)] ( P P P = 0.003). The sedation score was significantly higher in the BM group than in the B group at 15 min ( P = 0.001). In contrast, the duration of motor block after operation was similar in both groups. Conclusion The use of caudal magnesium sulfate (50 mg) combined with bupivacaine 0.25% was effective in reducing postoperative EA in preschool children undergoing hernia repair/orchiopexy procedures.

Summary Acute ethanol intoxication in rats pretreated with pyrogallol results in the formation of salsolinol in brain. Concentrations of the tetrahydroisoquinoline product of dopamine were estimated at ca.l7 ng/g in the combined midbrain, caudate nucleus and brain stem regions of pyrogallolethanol rats, or nearly 1% of the control dopamine concentrations. Salsolinol was not observable in rats given acute ethanol in the absence of pyrogallol, nor in pyrogallol controls given saline in place of ethanol. Furthermore, monoamine oxidase inhibition with pargyline in pyrogallol-saline and pyrogallol-ethanol rats produced significant increases in control brain dopamine and experimental brain salsolinol. Pyrogallol's facilitation of ethanol-dependent salsolinol biosynthesis is believed to be due principally to a potentiation of the blood levels of acetaldehyde derived from ethanol. In all ethanol experiments with pyrogallol-pretreated rats, brain concentrations of dopamine and norepinephrine were significantly depleted, presumably because of the increased acetaldehyde. This is the first demonstration of salsolinol in mammalian tissue during alcohol metabolism, although the alkaloid has been detected in urine of DOPA-treated Parkinsonian patients. It is conceivable that salsolinol, as a biologically active compound forming centrally in small amounts during certain chronic alcohol consumption situations, may have a role in the physical aspects of alcoholism.

A convenient method for the simultaneous gas chromatographic (GC) analysis of endogenous catecholamines (CA) and their alkaloid cyclization products with simple aldehydes, that is, catechol tetrahydroisoquinolines (TIQ) which may occur in vivo during alcoholism, has been developed. Catechol compounds are extracted from HClO4 supernatants of tissues with aluminum oxide, derivatized for GC analysis with heptafluorobutyryl (HFB)-anhydride at room temperature, separated on 5% GE XF-1105 or 3% OV-17 columns, and analyzed at picogram levels with a 63Ni electron capture (EC) detector. Levels of endogenous CAs in normal rat brain and in adrenals are readily determined with this method. If present in tissues, the TIQs derived from the cyclizations of acetaldehyde (AcH) with norepinephrine and epinephrine would be separated from their parent CAs on GE XF-1105, but salsolinol, the TIQ derived from dopamine (DA) and AcH, would require separation from DA on an alternate column such as 3% OV-17. The potential detection and analysis of salsolinol is particularly favored with this method because the HFB-derivative of salsolinol is very responsive to the EC detector. This method is applicable to small tissue samples and can be adapted clinically to serum and urine studies.

This paper summarizes some of our studies on the interactions of alcohol or amine-derived aldehydes with the catecholamines (CAs). There has been increasing research interest and speculation since 1968 in the potential formation of tetrahydroisoquinoline (TIQ) alkaloids in mammalian cells via such interactions, and in the role such TIQs may have in alcohol dependence. Reviewing, two principal TIQ theories related to alcoholism have been elaborated. (1) The initial suggestion is that ethanol (EtOH)-derived acetaldehyde (AcH) may produce “simple” (1-alkyl) TIQs from its bimolecular cyclization or condensation with CAs (Collins and Cohen, 1968; Robbins, 1968; Cohen and Collins, 1970; Yamanaka et al., 1970). The major products of these cyclizations, shown in Figure 1, are salsolinol derived from dopamine (DA), and the corresponding 4, 6, 7-trihydroxy-TIQ alkaloids derived from epinephrine (E) and nor-epinephrine (NE). For simplicity, the minor isomeric TIQs resulting from neutral aqueous cyclizations and stereochemical isomers of all products (Cohen and Collins, 1970; King et al., 1974) are not considered. (2) The second postulate depends upon the fact that EtOH-derived AcH, as a substrate for aldehyde dehydrogenase, may inhibit the oxidation and thereby elevate concentrations of endogenous phenylacetaldehydes which normally arise from DA and 3-methoxy-DA deaminations. Davis and Walsh (1970) suggested the EtOH-dependent augmentation of a TIQ formation route demonstrated in vitro a decade ago (Holtz et al., 1964), involving cyclization of the phenylacetal-dehydes with DA to give 1-benzyl-substituted-TIQs related or identical to tetrahydropapaveroline (Figure 1). Both theories suggest the alkaloids or their metabolites have neurophysiological actions that would persist after EtOH depressant effects had dissipated. These actions may be manifested in and underlie part of the alcohol withdrawal syndrome.