Molecular characterization of alpha subunit 1 of sodium pump (ATP1A1) gene in Camelus dromedarius: its differential tissue expression potentially interprets the role in osmoregulation.

BACKGROUND: Dromedary or one-humped camel (Camelus dromedarius) is distinctively acclimatized to survive the arid conditions of the desert environment. It has an excellent ability to compete dehydration with substantial tolerance for rapid dehydration. Therefore, it offers an excellent model for studying osmoregulation. Molecular characterization of Na+/K+ ATPase as a central regulator of electrolyte normohemostasis affords a better understanding of this mechanism in camel. Here is the first to resolve the full-length of alpha-1 subunit of sodium pump (ATP1A1) gene with its differential expression in dromedary tissues. RESULTS: The nucleotide sequence for the recovered full cDNA of ATP1A1was submitted to the GenBank (NCBI GenBank accession #MW628635) and bioinformatically analyzed. The cDNA sequence was of 3760 bp length with an open reading frame (ORF) of 3066 bp encoding a putative 1021 amino acids polypeptide with a molecular mass of 112696 Da. Blast search analysis revealed the shared high similarity of dromedary ATP1A1gene with other known ATP1A1genes in different species. The comparative analysis of its protein sequence confirmed the high identity with other mammalian ATP1A1 proteins. Further transcriptomic investigation for different organs was performed by real-time PCR to compare its level of expression among different organs. The results confirm a direct function between the ATP1A1 gene expression and the order of vital performance of these organs. The expression of ATP1A1 mRNA in the adrenal gland and brain was significantly higher than that in the other organs. The noticed down expression in camel kidney concomitant with overexpression in the adrenal cortex might interpret how dromedary expels access sodium without water loss with relative high ability to restrain mineralocorticoid-induced sodium retention on drinking salty water. CONCLUSION: The results reflect the importance of sodium pump in these organs. Na+/K+ ATPase in the adrenal gland and brain than other organs.

A study on IL8RB gene polymorphism as a potential immuno-compromised adherent in exaggeration of parenteral and mammo-crine oxidative stress during mastitis in buffalo.

The genetic markers in inflammatory responses during mastitis afford a reasonable way for improving milk production in the Egyptian buffalo breed. Among them is the interleukin 8 Receptor Gene (IL8RB) (CXCR2); a chemokine receptor gene augments the neutrophil migration during infection. To understand its role better during mastitis in Egyptian buffalos, twenty-five dairy animals representing the normal, sub-clinically, clinically and chronically affected buffalos were randomly selected from different districts. Screening criteria for mastitis were based on somatic cell count and California mastitis test assays on their milk samples. Biochemically, mastitis induced an increase in milk lactate dehydrogenase, alkaline phosphatase and catalase activities and serum malanoaldehyde concentration. The total antioxidant concentrations, however, decreased in serum and milk during mammary inflammation. The protein profiling of milk whey proved an accelerated mammary inflammatory influx of blood-borne proteins during mastitis. The genomic DNAs were extracted from blood samples and the CXCR2 sequence of 1246 bp covering a part of intron 1, exon 2 and a part of 3'UTR were submitted to Genbank (accession # KY399457.1). The study clearly defined the presence of four SNPs. Three were detected as synonymous substitutions in coding region and one in the 3'UTR region. Only SNP C/A at c.127 was found to be highly associated with mastitis. In conclusion, the results warrant the potential correlation between the genetic SNP variance for certain genes and the incidence of mastitis in buffalo breed.

A double-blind double-dummy study of citalopram comparing infusion versus oral administration.

BACKGROUND: This study compares antidepressant efficacy and tolerability of citalopram given either orally or as a slow drop infusion. METHODS: Citalopram (40 mg/day) was administered double-blindly as tablets or slow-drop infusion during the first 10 days and then open, orally, up to treatment Day 42. RESULTS: In 60 moderately to severely depressed patients, the Hamilton depression total score (17-items) at baseline was 23.9 and 23.6 in the active infusion (n = 30) and active tablet (n = 30) group, respectively. These scores dropped in both groups to 15.6 and 16.9 on Day 10, and to 10.3 and 10.2 on Day 42. Response rates (delta Hamilton > or = 50%) amounted to 33.3% and 17.9% on Day 10, and 66.2% and 63.3% on Day 42, without a relevant group difference in citalopram plasma concentration. CONCLUSION: Slow-drop infusion with citalopram shows a similar risk/benefit relationship to oral citalopram. The design of this study allowed us to evaluate pharmacological but not psychological factors which may contribute to response to slow-drop infusion.

Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 360 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using chi2, t, and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients (p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 (p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.

A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation.

Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4) were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them, 45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating Scale for Depression [HAM-D]) and continued their treatment for another week before being released from the study. The 24 nonresponders were randomized and comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400 mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For days 36 to 42, the patients of both subgroups were treated openly with Li (800 mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients responded to the CIT-Li combination, whereas 2 of 14 patients only responded to the CIT-Pl combination. This group difference reached significance (p < 0.05) on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was seen of a pharmacokinetic interaction between CIT and Li, and this combination was well tolerated. Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28. As evaluated at baseline, three patients (responders) were poor metabolizers of dextromethorphan and six patients (three responders and three nonresponders) of mephenytoin. On day 28, the ratio CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events.

A double-blind comparison of moclobemide and thioridazine versus moclobemide and placebo in the treatment of refractory, severe depression.

In a multicenter study of 78 severely depressed inpatients (44 women and 34 men; age range, 23 to 70 years), the efficacy, onset of efficacy, and tolerability of the reversible monoamine oxidase-A inhibitor moclobemide (450 mg/day) in combination with thioridazine (100 mg/day) were compared with those of moclobemide (450 mg/day) plus placebo. Patients enrolled met the DSM-III-R criteria for severe depression and had a severity score of at least 20 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Additionally, these patients had not responded to at least two standard antidepressants during the 2 years preceding screening and the mean duration of the current episode was 6 months. After a washout period of 3 to 5 days, patients were randomized to one of the two treatment groups, which at the outset had similar characteristics. Efficacy was assessed by the HAM-D, a depression observation rating for nurses, and a Clinical Global Impression (CGI) scale. Tolerability assessments included an overall rating, a description of adverse events, vital signs, electrocardiogram, and laboratory tests. After 4 weeks of therapy, both groups of patients showed significant improvements in HAM-D and CGI scores. The response rates (based on HAM-D > or = 50% decrease) were 74% for moclobemide/thioridazine and 77% for moclobemide/placebo, and according to CGI scores, 76 and 72% were "very much improved" or "much improved," respectively. Onset of effect was noted after 9.2 and 9.8 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of intermittent deep hypoxia on the adrenal gland cortex]. / Kora nadbubrezne zlezde u uslovima ponavljane duboke hipoksije.

Wister laboratory rats were subjected to decreased atmospheric pressure occurring at the height of 23000 feet every day during 4 days and every second day during 11 days. The effect of hypoxia on the adrenal cortex and biochemical blood factors in rats, sacrificed at different times after the completion of exposure to hypoxic conditions was investigated. The hypoxic stress elicited alkalosis when Pa O2 and Pa CO2 were decreased, while the saturation oh hemoglobin by oxygen was enhanced. The animals, which were exposed to hypoxia for 4 consecutive days, better endured the whole course of the experiment than those ones exposed every second day. The histological changes in the adrenal cortex were stronger in the animals exposed to the experimental conditions with two-day breaks. The intensity, character and reversibility of the changes depended much more on the rhythm of exposure than on the rhythm of sacrifice.

[Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes]. / Etude multicentrique comparant l'efficacité et la tolérance du moclobémide et de la fluvoxamine chez des patients hospitalisés et ambulatoires présentant un épisode dépressif majeur.

In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.

[Treatment of resistant depression with the citalopram-lithium combination. Methodology of a double-blind multicenter study and preliminary results]. / Traitement de la dépression résistante par l'association citalopram-lithium. Méthodologie d'une étude multicentrique en double aveugle et résultats préliminaires.

Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy-resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double-blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29-D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu

[The vascular network of the adrenal medulla in experimentally simulated altitude sickness]. / Vaskularna mreza nadbubrezne medule u uslovima eksperimentalno simulirane visinske bolesti.

Laboratory rats were exposed to the effect of intermittent hypoxia every second day over the 11-day period. Conditions characteristic of 7000 m of height above sea level were imitated. The effect of hypoxia on the adrenal medulla vascular network in rats, sacrificed at different times after the completion of exposure to hypoxic conditions, was investigated. Stereological percentage of the medulla blood vessels was 23% in the control group, 37% in the group with sacrificed rats immediately after the last exposure, and 45% in the group 4 days after the end of experiment. The obtained results showed that increased blood supply in the adrenal medulla was achieved during the experimental treatment.