Clinical efficacy analysis of preoperative neoadjuvant chemotherapy with high-dose dense paclitaxel plus cisplatin in Stages IB2, IIA2, IIB cervical cancer in Iran.

PURPOSE OF INVESTIGATION: In Iran, the authors use neoadjuvant chemotherapy (NACT) prior to surgery in cervical cancer due to limited access to the radiotherapy and very prolonged waiting time in accession to radiotherapy. The study was done to analyze the efficacy of the NACT with high dose-dense paclitaxel and cisplatin before radical surgery on cure rate, survival rate, and the progression of free survival rate of bulky tumor of cervical cancer in Stages 1B2, IId A2, and IIB. MATERIALS AND METHODS: Fifty-two patients with cervical cancer in Stages Ib2, IIA2, and IIB were selected, and responding patients to chemotherapy were scheduled to undergo radical hysterectomy and bilateral pelvic lymphadenectomy with or without para-aortic lymphadenectomy. RESULTS: Fifty out of 52 patients with a median age of 50 years were evaluable for clinical response. Thirty-two patients (64%) responded to the NACT including six (12%) with a complete clinical response. There was no statistical relationship between clinical response, tumor stage and size, and parametrical involvement, however, patients with higher grade of tumor, adenocarcinoma or tumor in upper 2/3 of vagina showed a higher probability of no response to chemotherapy. Downstaging after NACT in all stages was statistically significant regarding pathologic findings and clinical response (p = 0.002). Five-year survival was 88% and factors affecting survival and disease-free survival were pathological response and tumor site based on cox-regression analysis. Overall recurrence rate was 20% and tumor size was the only significant relevant factor for recurrence (p = 0.017). CONCLUSION: Combined regimen of chemotherapy in locally advanced cervical cancer proved to be valuable and efficacious without any late complications.

Mini review on blood-brain barrier penetration of pyridinium aldoximes.

This paper reviews the blood-brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration.

Aloe vera for prevention of radiation-induced dermatitis: a self-controlled clinical trial.

To evaluate an Aloe vera lotion for prevention of radiation-induced dermatitis, all patients with a prescription of radiotherapy to a minimum dose of 40 Gy were eligible provided that their treatment area could be divided into two symmetrical halves. Patients were given a lotion of Aloe vera to use on one half of the irradiated area, with no medication to be used on the other half. The grade of dermatitis in each half was recorded weekly until 4 weeks after the end of radiotherapy. The trial enrolled 60 patients (mean age: 52 years; 67% women). Most patients had breast cancer (38%), followed by pelvic (32%), head-and-neck (22%), and other cancers (8%). Field size was 80-320 cm(2) (mean: 177 cm(2)), and the dose of radiotherapy was 40-70 Gy (mean: 54 Gy). Concurrent chemotherapy was administered in 20 patients. From week 4 to week 6 of radiotherapy and then at weeks 2 and 4 after radiotherapy, the mean grade of dermatitis with and without Aloe vera was 0.81 and 1.10 (p < 0.001), 0.96 and 1.28 (p < 0.001), 1.00 and 1.57 (p = 0.006), 0.59 and 0.79 (p = 0.003), and 0.05 and 0.21 (p = 0.002) respectively. Age and radiation field size had a significant effect on the grade of dermatitis. Based on these results, we conclude that the prophylactic use of Aloe vera reduces the intensity of radiationinduced dermatitis.

Neoscytalidium dimidiatum as onychomycosis causative agent in an Iranian patient: a case report and literature review.

A 38-year-old healthy male presented to our medical mycology center with whitish opaque discoloration of the right toenail. He reported a history of some sand scratches subsequent to walking barefoot on the beach two years ago and wearing hard safety shoes for a period of two years. On clinical examination, onycholysis, onychodystrophy, and apparent thickening of the ungual bed in the left big toe were found. The microscopic examination of nail clippings using 15% potassium hydroxide (KOH/) revealed the presence of septate pigmented hyphae. The fungus was identified as Neoscytalidium dimidiatum based on the cultural characteristics, the arrangement of arthroconidia on lactophenol cotton blue (LPCB) staining, blocky-brown pigmented hyphae on serum physiology mounts, and sequencing. Susceptibility of the isolated fungi to amphotericin B, itraconazole, voriconazole, and terbinafine was tested using the standard broth microdilution M38-A2 method developed by the Clinical and Laboratory Standards Institute (CLSI). The minimum inhibitory concentrations (MICs) of the four antifungal drugs used in this study were: amphotericin B: 1 mg/L, itraconazole: 2 mg/L, voriconazole: 0.25 mg/L, and terbinafine: 1 mg/L. The patient underwent terbinafine and clobetasol topical treatments for 6 months.

Infected Viabahn stent graft in the superficial femoral artery.

We present a case of an infected stent graft in the superficial femoral artery (SFA). A 67-year-old woman underwent excision of an infected Viabahn stent graft. At exploration there was no apparent artery around the majority of the stent graft, suggesting that the SFA had been autolysed. Infected stents and stent grafts are rare in the SFA position. The risk of infection is likely minimised with standard treatments including drainage of infection prior to stent graft placement and periprocedural antibiotic administration. Successful management will, in most cases, require excision of the stent graft and adjunctive arterial reconstruction, as necessary.

Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: a double-blind placebo-controlled randomized clinical trial.

We evaluated the efficacy of benzydamine oral rinse for prevention of radiation-induced mucositis. Patients with head and neck cancers, who were referred in 2004-2005, received an oral rinse of either benzydamine or placebo. One hundred patients were randomized in this trial. At the end of the study, 19 patients were excluded from the analysis because they did not use the medication for the assigned period. In the benzydamine group, the frequency of mucositis grade > or =3 was 43.6% in contrast to 78.6% in other group (P = 0.001). Grade > or =3 mucositis was 2.6 times more frequent in the placebo group. Intensity of mucositis increased up to fourth week of treatment in both groups to grade 2. In the treated group the grade of mucositis was approximately constant to the end of therapy; but in the control group it raised to grade 3 (P < 0.001). The highest grade of mucositis during the treatment time was significantly different between two groups (P = 0.049). The median interval to observation of grade > or =2 mucositis was 24 days in the placebo group and 28 days in the benzydamine group (P = 0.12). Benzydamine oral rinse seems to be effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis in head and neck tumours.

Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients.

BACKGROUND: Despite high-level evidence in the literature, the use of single-fraction radiotherapy (rt) for management of painful bone metastases is not widely practiced in the world, as highlighted in several practice-pattern surveys. Fractionation of palliative rt for bone metastases has not been addressed in Iran, where the most common clinical practice is the use of 30 Gy in 10 fractions. Thus, we decided to perform a randomized clinical trial to compare responses in our patients with those reported in the international literature. PATIENTS AND METHODS: Adult patients with multiple painful uncomplicated bone metastases were randomized to 8 Gy in a single fraction or 30 Gy in 10 fractions. Pain was graded by the patients on a scale of 1 to 4 just before and again 1 month after the end of rt. Palliative response was defined as "complete" (pain reduction of 2 grades or more), "partial" (pain reduction of 1 grade or more, but less than 2 grades), and "no response" (pain reduction of less than 1 grade). RESULTS: We randomized 70 patients in this trial (63% women; mean age: 51.6 years). Sites of treatment included spine (n = 27), sacrum or pelvis (n = 25), extremities (n = 14), ribs (n = 3), and sternum (n = 1). Patients graded their pain before rt in a range from 1.8 to 4.0 (mean: 3.2). All patients finished their scheduled course of rt without incident. Unfortunately, 5 patients died less than 1 month after the end of rt, and 7 did not return for any follow-up and could not be contacted. As a result, only 58 patients (31 who received multiple fractions, and 27 who received a single fraction) were available for evaluation of pain 1 month after treatment. At that time, pain was graded in a range from 1.0 to 4.0 (mean: 2.0). The reduction in pain grade ranged from -0.8 to 2.6 (mean: 1.1). We observed 8 (14%) complete responses, 33 (57%) partial responses, and 17 (29%) no responses, for an overall response rate of 71%. The number of responders was 21 (78%) among those who received a single fraction and 20 (65%) among those who received multiple fractions (p > 0.1). The mean reduction in pain was 1.1 in both groups. The 10-fraction group contained a higher number of complete responders (11 of 31 as compared with 6 of 27 in the 1-fraction group)-a result that was not statistically significant. The mean reduction in pain was 1.4 in patients 50 years of age or younger and 0.9 in patients more than 50 years of age (p = 0.01). Of the 8 complete responses, 7 (87.5%) were seen in the patients 50 years of age or younger, and the mean age of patients with a complete response (38.7 years) was significantly lower than that of patients with a partial response or no response (53.7 years, p = 0.017). By logistic regression, patient sex, primary tumour, rt site, and type of treatment (single-fraction vs. multifraction) did not have any significant effect on pain reduction. The only factor with a significant effect was age (p = 0.002). CONCLUSIONS: Our trial showed no significant difference in pain relief after palliative radiotherapy with 1 or 10 fractions in Iranian patients. The overall response rate was 71%, similar to results in the international literature. Younger patients responded better.

Composition and antifungal activity of Zhumeria majdae essential oil.

BACKGROUND AND PURPOSE: Essential oils extracted from different plants are extensively used in perfume, beverage, and food industries and are reported to exhibit antimicrobial activities against a variety of fungi. Zhumeria majdae belonging to the Lamiaceae family is a rare and endemic medicinal plant species in Iran, with a strong and pleasant odor. The leaves of this plant have been used for many years as an antiseptic carminative agent for the treatment of stomachache (especially in infants) and dysmenorrhea. MATERIALS AND METHODS: Gas chromatography/mass spectrometry (GC/MS) analysis was performed to determine the main constituents of the essential oil extracted from the aerial parts of Z. majdae. Also, the minimum inhibitory concentrations (MICs) were determined, using serial dilution method. RESULTS: Based on the GC/MS analysis, 31 compounds representing 95.36% of the essential oil, extracted from the aerial parts of the plant, were identified, among which linalool (63.40%) and camphor (27.48%) were recognized as the major constituents. The total phenolic content was 42.74 GAE (mg)/DW (g). The hydro-distilled essential oil from the aerial part of the plant displayed potential antifungal activities against all the tested pathogenic fungal species (i.e., Candida albicans, Trichophyton mentagrophytes, Aspergillus flavus, Trichophyton rubrum, Microsporum canis, Microsporum gypseum, and Epidermophyton floccosum). Based on the inhibition zone (29 mm) and MIC value (0.015 µl/ml), all the tested strains were sensitive to Z. majdae essential oil. CONCLUSION: The present results support the traditional and possible use of Z. majdae essential oil in food, pharmaceutical, and cosmetic industries.

Opportunities of marker-assisted selection for rice fragrance through marker-trait association analysis of microsatellites and gene-based markers.

Developing fragrant rice through marker-assisted/aided selection (MAS) is an economical and profitable approach worldwide for the enrichment of an elite genetic background with a pleasant aroma. The PCR-based DNA markers that distinguish the alleles of major fragrance genes in rice have been synthesised to develop rice scent biofortification through MAS. Thus, the present study examined the aroma biofortification potential of these co-dominant markers in a germplasm panel of 189 F2 progeny developed from crosses between a non-aromatic variety (MR84) and a highly aromatic but low-yielding variety (MRQ74) to determine the most influential diagnostic markers for fragrance biofortification. The SSRs and functional DNA markers RM5633 (on chromosome 4), RM515, RM223, L06, NKSbad2, FMbadh2-E7, BADEX7-5, Aro7 and SCU015RM (on chromosome 8) were highly associated with the 2AP (2-acetyl-1-pyrroline) content across the population. The alleles traced via these markers were also in high linkage disequilibrium (R(2) > 0.70) and explained approximately 12.1, 27.05, 27.05, 27.05, 25.42, 25.42, 20.53, 20.43 and 20.18% of the total phenotypic variation observed for these biomarkers, respectively. F2 plants harbouring the favourable alleles of these effective markers produced higher levels of fragrance. Hence, these rice plants can be used as donor parents to increase the development of fragrance-biofortified tropical rice varieties adapted to growing conditions and consumer preferences, thus contributing to the global rice market.

Association of indicators of bacterial vaginosis with a female genital tract factor that induces expression of HIV-1.

OBJECTIVE: The aim of this study was to determine the relationship of bacterial vaginosis and bacterial vaginosis-associated microorganisms with an HIV-inducing factor (HIF) found in cervicovaginal lavage. DESIGN: A total of 26 cervicovaginal lavage specimens collected from 17 women were used in this study to determine if HIF was significantly associated with features consistent with bacterial vaginosis. METHODS: Patients were evaluated for various clinical features including age, HIV status and stage, CD4 cell counts, clinical diagnosis of gynecological infections, vaginal pH, Gram stains of vaginal fluid, phase of menstruation, and presence of cervical dysplasia. Cervicovaginal lavage specimens were analyzed for the presence of HIF by U1 bioassay. The presence of Gardnerella vaginalis, and general Mycoplasmataceae, and specifically Mycoplasma hominis, Ureaplasma urealyticum, M. fermentans, M. genitalium in cervicovaginal lavage were determined by semiquantitative PCR. RESULTS: Eleven cervicovaginal lavage samples from seven women were HIF-positive and 15 cervicovaginal lavage samples from 11 women were HIF-negative (patient No. 8 had two HIF-negative cervicovaginal lavage and one HIF-positive cervicovaginal lavage). The following parameters were significantly associated with HIF: abnormal vaginal fluid pH (>4.5) (P = 0.006), Gram stains indicative of bacterial vaginosis (P = 0.007), normal menstrual cycle (P = 0.0007) and PCR detection and relative quantity of M. hominis (P = 0.0003, P = 0.002). CONCLUSIONS: This study indicates that HIF is closely associated with features of bacterial vaginosis.

Myeloid-related protein (MRP)-8 from cervico-vaginal secretions activates HIV replication.

OBJECTIVES: To identify a substance found in female genital tract secretions that enhances HIV expression in infected cells. DESIGN: Cervico-vaginal lavages (CVL), collected in sterile normal saline, were fractionated and tested for HIV-inducing activity using HIV-infected monocytes. METHODS: To purify the component(s) of CVL that enhance HIV production, Mono-Q ion exchange chromatography followed by Superose-12 molecular sieve analysis, and SDS--PAGE were performed. The purified protein was identified by amino acid sequence analysis. RESULTS: SDS--PAGE of bioactive fractions showed a 14 kDa polypeptide band. Amino acid sequence analysis of selected peptides from the 14 kDa band showed 100% homology with the myeloid-related protein (MRP)-8, an inflammatory protein found in mucosal secretions. Western blot analysis revealed that bioactive CVL contained more immunoreactive MRP-8 than samples without bioactivity. The HIV-inducing activity of MRP-8 was further confirmed by showing that human recombinant MRP-8 increased HIV expression by up to 40-fold. CONCLUSIONS: MRP-8 in cervico-vaginal secretions stimulates HIV production. Strategies aimed at blocking MRP-8 activity in the genital tract could reduce risk of sexual as well as maternal--infant transmission of HIV.

Antigen-stimulated apoptotic T-cell death in HIV infection is selective for CD4+ T cells, modulated by cytokines and effected by lymphotoxin.

OBJECTIVE: To characterize the mechanism of in vitro antigen-induced apoptotic T-cell death in the peripheral blood mononuclear cells (PBMC) of HIV-1-infected individuals. DESIGN AND METHODS: PBMC from HIV-1 infected and uninfected individuals were unstimulated or stimulated with HIV-1 envelope synthetic peptides (Env) or influenza A virus to determine the extent of antigen-stimulated apoptotic T-cell death, whether this death was limited to the CD4+ subset, and the effects of cytokines on T-cell death. Death was assessed by apoptotic nuclear morphology after 7 days of culture by fluorescence microscopy using a DNA-specific dye. Transwell cultures and supernatant transfers were utilized to test whether a soluble factor produced by HIV-positive PBMC induced death of HIV-negative T cells. Exogenous cytokines [interleukin (IL)-12, interferon (IFN)-gamma, IL-4 and IL-10], as well as antibodies against endogenously produced cytokines (IL-4, IL-10, IL-12, and lymphotoxin) were tested for their ability to modulate death. RESULTS: Antigenic stimulation induced death in PBMC from HIV-positive donors, but not in PBMC from HIV-negative donors. Antigen-stimulated death was seen in CD4+ but not CD8+ T-cell subset from the HIV-positive patients. Apoptotic death was blocked by IL-12, IFN-gamma, anti-IL-4, anti-IL-10, and anti-lymphotoxin, but not by anti-IL-12. Transwell and supernatant transfer experiment indicated that antigen-stimulated HIV-positive PBMC produced a factor that killed T-cell blasts. The factor was inhibited by anti-lymphotoxin, but not by anti-IL-10. CONCLUSIONS: Stimulation of HIV-positive PBMC with CD4-dependent antigens results in selective death of CD4+ T cells that is modulated by cytokines. Our results suggest that apoptotic death is not limited to HIV-infected or HIV-specific T cells, but occurs in bystander cells. Lymphotoxin is a mediator of antigen-stimulated T-cell death in this in vitro model.

Human immunodeficiency virus induction of corticotropin in lymphoid cells.

Disruption of the linkage among the immune, nervous, and endocrine systems may contribute to the pathology and symptoms of acquired immunodeficiency syndrome (AIDS). We investigated the role of human immunodeficiency virus (HIV) in altering these linkages via induction of corticotropin (ACTH) by lymphocytes. Cultured T lymphocytes (H9 cell line) were infected with HIV-1, after which ACTH production was measured and characterized at various time intervals by immunofluorescence and Western blotting. We report a coordinate expression of ACTH and p24 HIV core protein in H9 cells. Also, the kinetics of HIV-induced ACTH production by H9 T lymphoma cells are demonstrated using three different strains of HIV as well as UV-inactivated HIV. ACTH production corresponded with the appearance of p24 antigen and was maximal 35 days after infection. UV-inactivated HIV and the viral envelope protein, gp120, were also able to induce ACTH production in these cells, indicating that viral replication was not required for the ACTH induction. The HIV-induced ACTH was synthesized de novo and had the size and biological activity of pituitary ACTH. Inhibition of ACTH in HIV-infected lymphocyte cultures by anti-ACTH antiserum enhanced viral p24 expression. The significance of lymphocyte ACTH in AIDS is not clear, but these results suggest that it may restrict HIV replication and possibly infection.

Detection and molecular mass determination of an HIV replication-enhancing female genital tract factor using a blot bioassay.

We previously reported that cervicovaginal lavages (CVL) contain a factor that enhances the replication of human immunodeficiency virus (HIV) by increasing virus transcription in T cells and monocytoid cells. This factor was named the HIV-inducing factor (HIF). To determine the molecular mass of HIF, we adapted a blot technique that involves nonreducing SDS-PAGE of CVL samples and electrophoretic transfer onto nitrocellulose paper followed by incubation of paper slices with HIV-infected monocytoid U1 cells. The slices with HIF bioactivity were detected by increased HIV production and measured by an HIV core protein (p24) ELISA. We refer to this technique as the "BioBlot" assay. The BioBlot assay successfully detected bioactivity of HIF anchored onto nitrocellulose and determined that HIF has a molecular mass of about 14 kDa. Paper slices with HIF-negative CVL samples as well as nitrocellulose paper samples without CVL did not enhance HIV production. This finding suggested that SDS-PAGE and nitrocellulose binding do not functionally alter the bioactive domain(s) of HIF structure. In addition to the detection of HIF bioactivity anchored to nitrocellulose and HIF molecular mass determination, the BioBlot technique offers an alternative, rapid method for other applications. These include the study of receptor-ligand interactions of mucosal proteins, direct bioactivity testing and molecular mass determination of secretory substances.

Pharmacological inhibition of forskolin-stimulated adenylate cyclase activity in rat brain by melatonin, its analogs, and diazepam.

Preincubation of rat forebrain membranes for 30-60 min with micromolar concentrations of the pineal hormone, melatonin, significantly inhibited forskolin-stimulated adenylate cyclase (AC) activity. Melatonin had an EC25 (concentration which inhibited AC activity by 25%) of 600 microM and caused a maximal inhibitory effect of approximately 30% at a concentration of 1000 microM. A comparison of the effects of melatonin and its analogs, 6-chloromelatonin and 2-iodomelatonin, in the striatum revealed that these halogenated drugs were 2-3 times more potent than melatonin in inhibiting AC activity. The EC25 values were 611, 226 and 189 microM for melatonin, 6-chloromelatonin and 2-iodomelatonin respectively. The receptor antagonists phentolamine (alpha-adrenergic), propranolol (beta-adrenergic), and metergoline (serotonergic) did not block the effect of melatonin in forebrain membranes. The central-type benzodiazepine (BZ) antagonist, Ro 15-1788 (flumazenil), also failed to block the inhibitory effects of melatonin, and the benzodiazepines, diazepam and Ro 5-4864, on AC activity. Evidence that inhibition of adenylate cyclase activity may be involved in the prevention of seizures suggests that the reported anticonvulsant effect of large doses of melatonin may be due to this mechanism. The greater potency of the halogenated melatonin analogs in inhibiting AC suggests that further study of their potential usefulness as anticonvulsants would be worthwhile.

Spectrophotometric determination of periodate or iodate ions by liquid-liquid extraction as an ion-pair using tetramethylammonium iodide.

A simple and accurate extractive Spectrophotometric procedure was developed for the microdetermination of periodate and iodate in aqueous media. The determination of periodate was based upon the extraction of the ion-pair formed between the periodate and tetramethylammonium iodide at pH 4 in chloroform followed by direct Spectrophotometric measurements at 509, 358 and 288 nm. The optimum concentration range evaluated by Ringbom's plot, the molar absorptivity, the Sandell's sensitivity and the stoichiometry of the formed ion-pair were critically determined. Iodate could be determined quantitively by the proposed procedure after oxidation to periodate with potassium persulphate. The effect of the diverse ions on the determination of the periodate and/or iodate by the proposed procedures was also investigated. The application of the method for the analysis of iodate or periodate in the artificial fresh water was successfully carried out.

HPLC determination of brain biogenic amines following treatment with bispyridinium aldoxime K203.

Effect of a new acetylcholine-esterase reactivator, K203 as a new potential antidote in organophosphate intoxications was studied on dopamine (DA), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in seven brain regions (cerebellum, spinal cord, hippocampus, hypothalamus, striatum, medulla oblongata and frontal cortex) of rats by an optimized and validated HPLC method. No significant change in brain level of these neurotransmitters was found either 15 or 60 min following treatment. However, when 5-HIAA/5-HT ratios were calculated as measure of turnover, significant decreases were found in the cerebellum, hippocampus, hypothalamus and the frontal cortex 15 min following K203 administration, but after 60 min only in the frontal cortex.

Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain: could oxytocin-induced labor cause pervasive developmental diseases?

Perinatal single-hormone treatment causes hormonal imprinting with lifelong consequences in receptor-binding capacity, hormone production as well as in social and sexual behavior. In the present experiments, newborn rats were treated with a single dose of oxytocin, and the levels of biogenic amines and their metabolites were studied in 8 different brain regions and in the sera when the male and female animals were 4 months old. Both dopaminergic and serotonergic neurotransmission was found to be significantly influenced. The levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole acetic acid metabolites decreased in the hypothalamus and striatum. Dopamine, serotonin, norepinephrine, and 5-hydroxytryptophol levels were hardly altered, and there was no difference in the epinephrine levels. The results show that dopamine and serotonin metabolism of hypothalamus and striatum are deeply and lifelong influenced by a single neonatal oxytocin treatment Oxytocin imprinting resulted in decreased dopamine turnover in the hypothalamus and decreased serotonin turnover in the hypothalamus, medulla oblongata, and striatum of females. As the disturbance of brain dopamine and serotonin system has an important role in the development of pervasive developmental diseases (eg, autism) and neuropsychiatric disorders (eg, schizophrenia), the growing number of oxytocin-induced labor as a causal factor, cannot be omitted.

Medicinal chemistry of antimigraine drugs.

Migraine is one of the most frequent neurological disorder with high impact on the quality of life. Primary headaches such as migraine are pathophysiologically complex disorders. The concept of the trigeminovascular system dysfunction in migraine has led to a number of drug discoveries dramatically changing the treatment options. Acute and prophylactic therapy targeting either the trigeminovascular system or central structures involve several groups of drugs with peculiar medicinal chemistry. In the proposed review up to date concept of treatment strategy, medicinal chemistry data of the drugs used will be summarized. The present review gives detailed information on drugs effective in aborting migraine attacks (by inhibiting prostanoid synthesis, are agonists of serotonin 5-HT1B/D receptors, on the recently introduced CGRP-receptor antagonists) and the drugs recommended for prophylactic treatment (selected beta-adrenergic receptor antagonists, Ca-channel inhibitors, antiepileptics, antidepressants). The pharmacokinetics, fate in the body (absorption, distribution, metabolism, excretion) and significant pharmacological effects as well as the recent bioanalytical methods for their determination are presented.