Bioinformatics analysis reveals potential candidate drugs for psychological stress in ovarian cancer.

BACKGROUND: Women with ovarian cancer may be at increased risk for psychological distress around the time of diagnosis relative to patients diagnosed with other cancers, because of the seriousness of the disease. However, the molecular mechanism of this effect is far from clear. AIM: We sought to investigate the influence of psychological status in regulating gene expression among women with primary ovarian cancer and to identify the small molecules which exhibit similar effects with different psychological status. MATERIALS AND METHODS: DNA microarray analyses of 10 ovarian carcinomas (GSE9116, downloaded from GEO) identified 916 human transcripts that were differentially expressed in tumors from patients with high depression relative to grade-and stage-matched tumors from low depression patients, and pathways related to immune system were dysfunctional. RESULTS: Our results suggest that psychosocial stress is related to impaired immunity in ovarian cancer patients. Besides, we identified a group of small molecules which can be exploited as adjuvant drug to improve therapeutic effect for ovarian cancer, such as MS-275 and adiphenine. CONCLUSIONS: Our findings may be useful for the development of management strategies for psychological distress, and we suggest that there is a need for improvement in the quality of life of cancer outpatients being treated with chemotherapy.

Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

Condensed bridgehead nitrogen heterocyclic system: synthesis and pharmacological activities of 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid.

Several 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles were prepared by condensation of 4-amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles (3a,b) with various substituted aromatic acids and aryl/alkyl isothiocyanates through a one-pot reaction. These compounds were investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to those of ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

Pharmacologic treatment of detrusor incontinence with thiphenamil HCl.

A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

[Electric stimulation of the dental pulp in the evaluation of the central effect of analgesics]. / La stimolazione elettrica della polpa dentaria nella valutazione dell'effetto centrale degli analgesici.

We conducted a double-blind cross-over study in ten volunteers aged from 19 to 30 years, to compare the pain control effects of a single oral dose of two analgesic compounds (drug A: propyphenazone mg 250, ethylmorphine mg 5, caffeine mg 5; drug B: dipyrone mg 500, diphenhydramine mg 12.5, adiphenine mg 5, ethyl aminobenzoate mg 2.5) in an experimental pain model using stimulation of dental pulp. Constant voltage stimuli were delivered through silver chloride electrodes placed in contact with the vestibular surface of the upper medial incisor. At the beginning of the session, the pain input was graded by asking the subject to identify the weakest stimulus perceived (threshold level) and the strongest stimulus endurable (tolerance level). The range between threshold and tolerance level was divided in nine steps plus a subliminal step. The ten steps were delivered randomly, and each series of steps was repeated eight times. The subjects were instructed to rate the pain sensation in an arbitrary scale of 5 degrees. The procedure was repeated at 60 min and 180 min after drug administration. Each subject received two tablets of drug A or drug B in two different sessions at weekly intervals. Statistical analysis of the procedures showed that neither drug A nor drug B significantly affected the pain threshold. Drug A significantly reduced the total pain score (P less than 0.01) and its action peaked 60 min after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhibition of the metastasis of Lewis lung carcinoma in mice by the administration of spasmolytin, midantan and L-DOPA]. / Tormozhenie metastazirovaniia kartsinomy legkogo L'iuis u myshei pri vvedenii spazmolitina, midantana i L-DOFA.

Different combinations and doses of neurotropic drugs of the central action (spasmolytine, midantane, L-DOPA) coupled with the surgical removal of the lung Lewis carcinoma were studied for their effect on the metastatic spreading in C57BL/6 mice. It has been established that the long-term use of spasmolytine and midantane before and after the operation inhibits the metastatic process, that is expressed in the total volume reduction of lung metastases, lack of metastases in a number of mice and augmentation of the average life. Such method of drug application is more effective in the metastatic growth inhibition as against their application only in the pre- or postoperation periods as well as with the use of the other neurotropic drug combinations.

Estudo comparativo entre cetoprofeno e a associaçäo metamizol/adifenina/prometazina (MAP) na dor pós-operatória / A compartive trial with ketoprofen and the association matamizole/adifenine/prometazine (MAP) on postoperative pain

Cinqüenta pacientes adultos, submetidos a cirurgia corretiva de herniaçöes da parede abdominal, foram incluídos neste estudo aberto, objetivando comparar a açäo antiálgica do cetoprofeno (100 mg) a associaçäo metamizol, adifenina, prometazina (MAP) administrada em dose única por via intramuscular. Após a administraçäo, os pacientes foram observados, quanto ao alívio da dor, através de uma escala analógica visual e verbal (0 = sem dor e 4 = dor insuportável), nos tempos 30', 1, 2, 3, 4, 5, 6, 8, 10 e 12 horas. Näo foi permitido o uso de qualquer outro medicamento durante este período de observaçäo. Houve predominância do sexo masculino em ambos os grupos, sem diferença significativa entre os grupos. A idade média foi de 42,2 e 40,8 anos para os grupos cetoprofeno e MAP, respectivamente, tendo sido considerados homogêneos sob o ponto de vista estatístico. A hérnia inguinal foi o achado mais freqüente: 42,30% no grupo cetoprofeno e 64% no grupo MAP. Os grupos foram homogêneos quanto aos sinais vitais, sem apresentar alteraçöes significativas a herniorrafia, sendo que um através de anestesia geral e os demais 49 através de raquianestesia. A eficácia mostrou um resultado significativo. (p < 0,05) para o grupo cetoprofeno, já a partir da 1ª hora do estudo. A exemplo da escala analógica, a escala verbal também apresentou uma melhora significativa entre os grupos, quanto ao alívio da dor, já a partir da 1ª hora, com o grupo cetoprofeno apresentando melhores resultados. O efeito terapêutico foi considerado como exelente/bom em 100% dos casos no grupo cetoprofeno e 20% no grupo MAP, resultado este altamente significativo (p < 0,01). Todos os pacientes do grupo cetoprofeno concluíram o período de observaçäo. No grupo MAP, um paciente foi retirado por reaçäo urticariforme iniciada uma hora após a injeçäo e dois outros por ineficácia na 2ª hora pós-tratamento. Concluímos que, dada a melhor "performance" analgésica do cetoprofeno no pós-operatório imediato nas cirurgias na parede abdominal, esta parece ser uma droga muito útil nestes tipos de procedimentos, nos quais uma açäo analgésica imediata se faz necessária

[Trial of cholinesterase reactivators as proserine antagonists]. / Ispytanie reaktivatorov kholinésterazy kak antagonistov prozerina.

HI-6 and TMB-4 were the most effective and safe of 7 cholinesterase reactivators tested as agents for the prophylaxis of proserine poisoning of male mice. The reactivator HI-6 strongly potentiated the prophylactic efficacy of a mixture of atropine and arpenal administered in the doses sufficient for the blockade of both the m- and h-cholinoreactive systems of mice. As demonstrated by experiments in vitro, HI-6 and TMB-4 did not reacivate proserine-inhibited cholinesterase. The natural anticholinesterase activity of HI-6 was negligible. Based on the correlation of the data obtained to the reported data indicating that HI-6 has a low ganglioblocking activity it is inferred that the direct effect on the receptor is of no importance for the potentiating effect. It is assumed that HI-6 modulates the cholinoreactive systems, which leads to a dramatic increase of the efficacy of cholinolytics.

[Effect of N- and M- cholinoblockaders on experimental epileptogenesis]. / Vliianie N- i M-kholinoblokatorov na éksperimental'nyi épileptogenez.

It has been shown in chronic experiments on rabbits with epileptogenic foci provoked by microinjections of penicillin into the dorsal hippocamp that the N-cholinoblockers gangleron (3 mg/k, intravenously) and etherophen (5-10mg/kg, intravenously) possess marked anticonvulsant activity. Diphenin (50 mg/kg, intraperitoneally) was less potent. The M-cholinoblocker methamizil (1 mg/kg, intravenously), on the contrary, potentiated the epileptiform seizures. Emphasis is laid on the necessity of the goal-oriented synthesis and search for agents that would exhibit a "purely" central N-cholinoblocking action with a purpose of applying such agents as antiepileptic drugs. It is not recommended using the M-cholinoblockers for such purposes.

[Reproduction of "passive" avoidance in rats by administering pharmacologic agents]. / Vosproizvedenie "passivnogo" izbeganiia u krys s pomoshch'iu vvedeniia farmakologicheskikh agentov.

In experiments on rats learned to passive avoidance reaction in one trial with subsequent administration of electroconvulsive shock (two hours after learning), the influence of different factors on the retrieval of the lost reaction was tested after three days. The greatest restoring capacity was exhibited by a non-specific reminding agent, the bell, gamma-amino-butyric acid (200 mg/kg) and etimizol (1.5 mg/kg). In animals with a preserved reaction, a number of pharmacological agents impaired retrieval of the habit (caffeine 5 mg/kg, carbocholine 0.01 mg/kg and metamizil 0.5 mg/kg). Optimal conditions for the restoration of the lost reaction were formed by etimizol and gamma-aminobutyric acid. Cholinergic mechanisms play a certain role in the functioning of the retrieval apparatus.

[Use of acetylcholinesterase reactivators and central cholinolytics in the treatment of experimental tetanus poisoning]. / Primenenie reaktivatorov atsetilkholinésterazy i tsentral'nykh kholinolitikov pri lechenii éksperimental'noi stolbniachnoi intoksikatsii.

Experiments were conducted on rabbits with tetanus intoxication induced by the intravenous injection of a lethal dose of the toxin; a study was made of the therapeutic efficacy of the acetylcholinesterase reactivators--dipyroxim and isonitrosine, and also of the central cholinolytics--amizyl and diphacyl. In dose of 25 mg/kg dipyroxim produced no therapeutic effect, and in doses of 30--40 mg/kg caused the animal death. Amizyl and diphacil in a dose of 3--4 mg/kg caused elimination of tonic convulsions for 1 1/2--2 hours. As to isonitrosin--it produced the same effect for 4--5 hours. In case of combined administration of reactivators and cholinolytics convulsions were eliminated for 4--5 hours.

[Effect of several neuroleptic, adreno-, sympatho- and cholinolytic substances on the development of experimental cerebral edema induced by nicotine]. / Vliianie nekotorykh neirolepticheskikh, adreno, simpato- i kholinoliticheskikh veschestv na ravitie éksperimental'nogo oteka mozga, vyzvannogo nikotinom.

The influence of some neuroleptic, adreno, sympatho- and cholinolytic substances on the development of experimental brain edema induced with nicotine was studied in tests conducted on rats. It was ascertained that marked antiedemic properties display drugs blocking the alpha-adrenoreceptors (phentolamine, dopegit), the neuroleptic chlorpromazine and central M-cholinolytics (benactizine). Weak action exert central H-cholinolytics (difacil trasentin) and the neuroleptic galoperidol. Sympatho- and beta-adrenolytics (guanethidine, alpha-methyltyrosine, obsidan), and also the neuroleptic triphthazine fail to prevent the development of an experimental brain edema. It is presumed that a brain edema induced with nicotine comes as a result of the catecholamines liberation and is also due to stimulation of alpha-adrenoreactive systems.