Association of single-nucleotide polymorphism of melanocortin gene with feed intake in rabbit (Oryctolagus cuniculus).

The aim of the study was to investigate the association of two parts of melanocortin gene (MC4R-1, MC4R-2) and feed intake for V-line rabbits. V-line rabbits were grouped into high and low daily feed intake during the period from 30 to 63 days of age in order to identify MC4R SNPs useful for association study with feed intake. DNA from blood samples of each group was extracted to amplify the MC4R gene. The purified PCR products were sequenced in those had the highest and lowest feed intake. Alignment of sequence data from each group revealed that there is a variation detected in MC4R-1 at nucleotide 35 (T-G) (sense mutation) and another variation was detected in MC4R-2 gene at nucleotide 19 (T-C) (sense mutation) for high feed intake rabbits. These sense mutations lead to transform some amino acids and cause a significant change of the MC4R function. The results of average daily feed intake (ADFI) indicated that group (1) had significantly higher feed intake than group (2) of V-line rabbits. The detected mutations and the analysis of daily feed intake means revealed a significant association between MC4R polymorphism and feed intake in rabbits.

Genetic study of blepharoptosis among Egyptians.

OBJECTIVES: This study was aimed to develop an etiological classification of congenital blepharoptosis among Egyptian children and also to differentiate between congenital blepharoptosis as an isolated anomaly or part of a syndrome. BACKGROUND: Blepharoptosis refers to dropping of the upper eyelid. The difference in the height of the fissures with the eyes in primary position signifies the amount of ptosis. Ptosis has traditionally been divided into congenital and acquired types. METHODS: Thirty six patients presenting with blepharoptosis (22 males and 14 females) were examined. All patients were subjected to thorough detailed personal and family history, three generation family pedigree construction, and detailed clinical examination with complete eye evaluation. Investigations such as cytogenetic studies, EEG, ECG, EMG, X-ray, and MRI were done needed. RESULTS: Patients were classified into 4 groups: I--simple congenital ptosis (28%), II--blepharophimosis-ptosis-epicanthus inversus syndrome (25%), III--congenital fibrosis of extraocular muscles (CFEOM) (14%), IV--ptosis associated with syndromes (33%). CONCLUSIONS: Clinical aspects of blepharoptosis are related to etiology. The ophthalmologist should be alert for the possibility of coexisting associated defects (ocular and systemic) in patients with blepharoptosis. Genetic evaluation of patients with blepharoptosis is important to allow accurate diagnosis and to permit appropriate counseling on potentially life-threatening health issues (Tab. 5, Fig. 4, Ref: 37).

Revisiting an ancient treatment for transphincteric fistula-in-ano 'There is nothing new under the sun' Ecclesiastes 1v9.

OBJECTIVE: The history of treatments for fistula-in-ano can be traced back to ancient times. Current treatment of transphincteric fistulae is controversial, with many options available. We reviewed the history of treatment using cutting setons and present our series of transphincteric fistulae in the light of the series in the literature. DESIGN: Literature review and case series. SETTING: Hospital based coloproctology service PARTICIPANTS: 140 consecutive patients presenting with fistula-in-ano were included. MAIN OUTCOME MEASURES: The literature pertaining to treatment of transphincteric fistula was reviewed, along with the outcome of various treatment methods for this condition. Data were collected for 140 consecutive patients presenting with fistula- in-ano were assessed for fistula healing, recurrence and complications. RESULTS: A total of 140 consecutive patients with fistula-in-ano were identified, of which 111 were cryptoglandular (79.3%). Eighty-one of these 111 were transphincteric (73.0%). At a median follow-up of 35 months (range, 2-83 months), 70 transphincteric fistulae had healed (86.4%), 10 were still undergoing treatment (12.3%) and one patient was lost to follow-up prior to treatment (1.2%). Two patients in this group required a stoma (2.5%), six patients developed recurrence (7.4%); three 'true' recurrences (3.7%). One (1.2%) developed a chronic fissure. There were no reported cases of incontinence. CONCLUSIONS: The management of transphincteric fistula-in-ano is complex and controversial, for which no clear surgical procedure has gained acceptance as the gold standard. This study demonstrates that transphincteric fistulae can be successfully treated using cutting setons. A high healing rate (86.4%), low recurrence rate (7.4%) and a low complication rate (3.7%) are shown, which compares favourably with published rates over a long follow-up.

Etiology of catheter-associated sepsis. Correlation with thrombogenicity.

A series of 94 central venous catheters was observed at removal for gross evidence of intraluminal or surface thrombus deposition. All those that were later found to have positive cultures had been noted to display thrombus formation, while catheters having negative cultures were usually free of thrombus. Devices made of a relatively nonthrombogenic material (ethylene acrylic acid) were also relatively free of bacterial contamination.

Synthesis and biological investigations of some 5H-1,3,4-oxadiazolo[3,2-a]pyrimidin-5-ones.

The synthesis of some substituted 7-hydroxy-5H-1,3,4-oxadiazolo [3,2-a]pyrimidin-5-ones, a class of bicyclics with unexplored pharmacotoxicological properties, is described. Reacting the 2-phenyl derivative with bis(2,4,5-trichlorophenyl)benzylmalonate afforded a linear pyrano-oxadiazolopyrimidinedione. The assigned structures were verified by IR, 1H-NMR, and mass spectral studies. Six compounds of the series were screened for in vitro antibacterial and antifungal activities. The effect of four compounds on alkaline phosphatase enzyme was also examined.

Potential antineoplastics I: substituted 3,5-dioxo-and 3-thioxo-5-oxo-2,3,4,5-tetrahydro-1,2,4-triazines.

The synthesis of some 6-substituted 3,5-dioxo- and 3-thioxo-5-oxo-2,3,4,5-tetrahydro-1,2,4-triazines for possible antineoplastic activity is reported. The assigned structures were substantiated by IR, NMR, and mass spectral studies of representative members of the series. Four compounds were tested against P-388 lymphocytic leukemia and were inactive.

Synthesis of methaqualone and its diphasic titration in pure and tablet forms.

A one-step synthesis of methaqualone from N-acetylanthranilic acid and o-toluidine in the absence of a catalyst is described. A rapid diphasic titration procedure for its microestimation in pure and tablet forms, using dioctyl sodium sulfosuccinate and dimethyl yellow screened with oracet blue B, is proposed. The data were compared with those obtained from nonaqueous titration methods.

Relationship between shell porosity, shell thickness, egg weight loss, and embryonic development in Japanese quail eggs.

Japanese quail eggs that hatched (H) or pipped (PIP) exhibited less weight loss through 15 d of incubation than did eggs that died late (LD), whereas eggs containing early dead (ED) embryos exhibited the greatest weight loss. The pore concentration at the large end of each egg was greatest in H eggs when compared with all other types. The pore concentration at the equator was greatest in H eggs and least in the eggs of the ED embryos. All other egg types lay statistically between these two types with regard to equator porosity. The small end pore concentration was similar in H, INF, and LD eggs and in the LD, PIP, and ED eggs. The least number was exhibited by the ED eggs and most by the H eggs. The thinnest shells at the small end were exhibited by H eggs, whereas thicker small end shells were exhibited by ED, LD, and PIP egg types. No differences were observed at the large end or equator. The data suggest that ED eggs exhibit excessive weight loss even though shell porosity was lower and shell thickness was similar to other egg types. This suggests that some functional component of the egg such as the shell membrane or albumen may contribute to this excessive weight loss. A similar statement can be made for LD eggs, which experienced greater weight loss through 15 d than did PIP or H eggs.

Reactions with pyrrolidine-2,4-diones, III (1). Synthesis of some substituted 3-pyrrolin-2-ones and 4-hydrazonopyrrolidin-2-ones as potential antineoplastic and antimicrobial agents.

The syntheses of 3-bromo-, 3-substituted aminomethyl-, and 3-(4-substituted sulfamylphenylazo)-4-hydroxy-1,5-diphenyl-pyrrolin-2-ones 4,6 and 8 from 1,5-diphenylpyrrolidine-2,4-dione 3 via bromination aminomethylation and diazocoupling, respectively, are described. The preparation of some 1,5-diphenyl-4-(substituted thiosemicarbazono) pyrrolidin-2-ones 10 and their conversion either to 1,5-diphenyl-4-(substituted thiazol-2-ylhydrazono)pyrrolidin-2-ones 12 or to 1,5-diphenyl-4-(3,4-disubstituted-4-thiazolin-2-ylidenehydrazon o)pyrrolidin-2- ones 13, is also reported. Nine compounds were screened against P-388 lymphocytic leukemia in mice but were inactive. Two compounds (6a and 6b) exhibited in vitro activities against some Gram-positive bacteria.

Synthesis of tenuazonic acid analogues.

The synthesis of two 1.5-diaryltetramic acids, aryl analogues of tenuazonic acid, is described. The reactivity of position 4 of these tetramic acids towards primary and secondary amines, and o-methylation led to the synthesis of 4-substituted-delta3-pyrroline-2-one. Further, reactivity of position 3 has been indicated by the formation of 3-arylidenepyrrolidine-2.4-diones and by diazo-coupling. The structures assigned to the new compounds are substantiated by IR and NMR data.

Polysubstituted pyrazoles. Part 2: Sulphonamidophenylhydrazone-2-pyrazolin-4-ones and sulphonamidophenylazopyrazoles as potential anticancer agents.

The synthesis of some new derivatives of 1-[4-nitrophenyl]-5-[4-substituted sulphonamidophenylhydrazono]-2-pyrazolin-4-ones and 3,5-dimethyl-4-[4-substituted sulphonamidophenylazo]-pyrazoles is described. Bromination of ethyl 2-[nitrophenylhydrazono]-3-oxobutyrates in dry benzene afforded the 4-bromo derivatives which upon cyclization gave high yields of the 4-hydroxpyrazoles. Many other new intermediates were prepared and the results of the UV and IR spectral studies are discussed.

Synthesis of 1-cyano-2-hydroxy-4-quinolizinones and corresponding 5-cyano-4-hydroxy-2-pyridones. Part 187: Synthesis of heterocycles. Part 9: Quinolizines and Indolizines.

Active malonic esters condense with 2-pyridylacetonitrile giving 1-cyano-3-substituted 2-hydroxyquinolizin-4-ones. Catalytic hydrogenation of the resulting products led to the corresponding 1-cyano-3-substituted-2-hydroxy-6.7.8.9-tetrahydroquinolizin-4-ones. On the other hand, condensation of the active malonic esters with beta-aminocrotononitrile afforded 5-cyano-3-substituted-4-hydroxy-6-methylpyridine-2-ones. The IR and NMR data are reported.

Novel indolene-spiro-hydroxytetronimides as potential antineoplastic and antiviral agents.

In a continuing search for new antineoplastic and antiviral agents, the preparation of some substituted indol-2(3H)-one-3-spiro-2'-3',4'-dihydroxy-5'-imino-2',5'-dihydrofurans was designed. The synthesis was achieved by reacting isatin, 1-alkyl- or 1-aralkylisatin derivative with glyoxal sodium bisulfite and potassium cyanide. However, when 1-substituted aminomethyl derivatives of isatin or of 5-bromoisatin were used in this reaction, the indolone-spiro-hydroxytetronimide unsubstituted at position 1 was, unexpectedly, the only product isolated. Two compounds were tested against P-388 lymphocytic leukemia in mice and were inactive.

Synthesis of substituted 7-hydroxy-5H-1.3.4-thiadiazolo[3.2-a]pyrimidin-5-ones with anticipated antimicrobial activity.

The synthesis of some derivatives of substituted 7-hydroxy-5H-1.3.4-thiadiazolo[3.2-a]pyrimidin-5-ones, as possible antimicrobial agents, is described. The IR, NMR and MS data of representative members of the series are reported. Proposed common fragmentation pathways for this series are deduced.

Novel benzimidazoles with potential antimicrobial and antineoplastic activities.

The synthesis of some substituted 4-[1-(1-(1H-benzimidazol-2-yl) alkylamino]-1,5-dihydro-2H-pyrrol-2-ones and 3-[1-(1H-benzimidazol-2-yl)alkyl]-2-substituted-4(3H)-quinazolinon es is described. Five compounds displayed in vitro antibacterial and antifungal activities. Three of these compounds were tested against P-388 lymphocytic leukemia in mice and were inactive.

Reactions with pyrrolidine-2,4-diones, Part 4: Synthesis of some 3-substituted 1,5-diphenylpyrrolidine-2,4-diones as potential antimicrobial, anti-HIV-1 and antineoplastic agents.

The condensation of 1,5-diphenylpyrrolidine-2,4-dione (1) with ethyl orthoformate yielded 3-ethoxymethylene-1,5-diphenylpyrrolidine-2,4-dione (2). Reaction of the latter with hydrazine hydrate, secondary amines 7a-c or urea afforded the corresponding 3-substituted aminomethylene-1,5-diphenylpyrrolidene-2,4-diones 3, 8a-c or 9. On the other hand, condensation of 3 with veratraldehyde (5a) yielded 3-[(3,4-dimethoxybenzylidene)hydrazinomethylene]-1,5-diphenylpyrrolidine- 2,4-dione (6). Whereas, cyclization of 9 with the reactive malonate ester 11 produced 3-[(5-butyl-4-hydroxy-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-1-yl) methylene]-1,5-diphenylpyrrolidine-2,4-dione (12). The condensation of some selected aromatic aldehydes 5a-c and addition of morpholine (7c) or piperidine (7d) to some of the resulting 3-arylidene-1,5-diphenylpyrrolidine-2,4-diones 13b, c gave the respective 3-substituted methyl-4-hydroxy-1,5-diphenyl-delta 3-pyrrolin-2-ones 14a-c. Selected members of the new series were screened for their in vitro antimicrobial, anti-HIV-1 and antineoplastic activities. Two compounds 14a, b showed pronounced inhibitory activities against Gram-positive bacteria; whereas, in the in vitro anti-HIV-1 screening, only one compound 13c displayed a moderate activity. However, in the antineoplastic screening protocol, the tested compounds were devoid of activity.

Polysubstituted pyrazoles, Part 4: Synthesis, antimicrobial and antiinflammatory activity of some pyrazoles.

As a continuation of an earlier interest in polysubstituted pyrazoles, the synthesis of some derivatives of 1H-pyrazol-4-yl-2-oxo-but-3-enoic acid and ethyl 4-hydroxy-1H-pyrazole-3-carboxylates of potential antimicrobial and antiinflammatory activity is described. One compound showed in vitro antibacterial activity and two compounds displayed in vivo antiinflammatory potency in rats.

Synthesis of some pyridone derivatives.

Chlorination of 6-aryl-3-cyano-2-pyridone-4-carboxylic acid (1) afforded the corresponding acid chloride (2) and the 2-chloro derivative (3). Esterification of (2) gave the corresponding esters (4a; b). Hydrazinolysis of (4a) afforded the respective pyridazinone derivative (5). Treatment of 6-aryl-2-chloro-3-cyano-4-pyridine carboxylic acid (3) with acetyl hydrazine, gave the triazinopyridine derivative (6), while treatment of 3 with sodium azide in DMF afforded the tetrazinopyridine derivative (7). Treatment of the N-acetyl derivative (1b) with thiosemicarbazide and/or hydroxylamine hydrochloride, yielded the correspoding semicarbazone and oxine derivatives (8) and (10), respectively. The reaction of 6-aryl-3-cyano-1,2-dihydro-2-thioxo-4-pyridinecarboxylic acid (1c) with ethylchloro acetate and/or thiourea yielded the mercapto ester derivative (11) and the corresponding pyrido [2,3-d] pyrimidine thione derivative (12). Condensation reaction of (1d) with anthranilic acid, afforded the quinazolone derivative (11). The reactivity of 11 towards hydrazine hydrate was investigated. The structural assignment of the new derivatives were based on IR, 1H NMR and mass data. Some of the new compounds were screened, in vitro, for antimicrobial activity and the results were encouraging.

Effect of garlic on lead contents in chicken tissues.

Lead has been indicted to be involved in the aetiology of human and animal diseases. In view of earlier literature indicating that garlic antagonized lead toxicity, we have investigated the possible use of garlic feeding to clean up lead contents from chickens which had been exposed to natural or experimental lead pollution and consequently eliminate one of the sources of lead pollution to human consumers. Groups of chickens (10 birds each) were given lead alone (lead acetate equivalent to 5 mg lead/kg B.W.) or both lead and garlic simultaneously or lead followed by garlic post-treatment or garlic alone or distilled water. Lead concentrations were reduced in muscle and liver tissues of chickens given both lead and garlic simultaneously or as a post-treatment. Reduction in tissue-lead concentrations were greater in birds given garlic as a post-treatment than those given garlic simultaneously with lead. The results indicate that garlic contain chelating compounds capable of enhancing elimination of lead. Garlic feeding can be exploited to safeguard human consumers by minimizing lead concentrations in meat of food animals which had been grown in a lead polluted environment.