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.

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.

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.

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.

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.

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.

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.

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.

Plasma concentrations of PGFM and uterine and ovarian responses in early lactation dairy cows fed omega-3 and omega-6 fatty acids.

A total of 120 dairy cows were assigned randomly to three diets to determine the effects of omega-6 or omega-3 fatty acid (FA) supplementation on uterine diseases, ovarian responses, and blood concentrations of estradiol, progesterone, and PGFM in lactating Holstein dairy cows. Diets contained either protected palm oil (C), extruded linseed (L), or roasted whole soybeans (S), and they were fed from calving to Day 70 postpartum. Estrous cycles were synchronized and ovarian follicular development was monitored daily for an entire cycle. There were no differences among diets in the incidence of lameness, mastitis, or metritis, but the incidence of clinical endometritis was lower (P < 0.05) in cows fed S (0%) compared with cows fed C (28.2%) and L (20.5%). Uterine involution in cows fed S occurred 3.77 and 2.78 days earlier, respectively, than in those fed C and L. The PGFM response 60 minutes after an oxytocin challenge was highest for cows fed S and lowest for cows fed L. Mean plasma progesterone concentration on Day 15 of the synchronized cycle was higher in cows fed S (14.5 ng/mL) and L (15.0 ng/mL) than in those fed C (12.0 ng/mL). The ovulatory follicle on Day 21 of the estrous cycle (estrous = Day 0) was larger in cows fed S (16.1 ± 0.9 mm) and L (15.7 ± 0.7 mm) compared with cows fed C (13.2 ± 0.87 mm; P = 0.02) but there were no significant differences between cows fed diets S and L. The mean number of small and medium follicles and diameter of subordinate follicle were similar among diets. In conclusion, feeding a source of omega-6 FA can be a strategy to improve uterine health after calving, although a source of omega-3 FA such as L should be fed after uterine involution to decrease PGF2α secretion.

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 drugs with active metabolites (N-, O-, and S-desalkylation and some specific oxidative alterations).

Metabolic fate plays an important role in the elimination of drugs and other foreign compounds from the body. Metabolism through various enzyme systems, makes the parent compound more hydrophilic, thus, it can be readily excreted from the body. Some active metabolites of drugs are produced following N-, O-, and S-desalkylation. These metabolites are either more or less potent, or as potent as their parent drugs. The removal of alkyl groups from tertiary aliphatic and acyclic amines is carried out by hepatic cytochrome P450 mixed-function oxidase enzymes. Several drugs undergo this process, which yields free hydroxyl-, or amino-groups, in addition to aldehyde from the splitted alkyl group. Metabolism of drugs into clinically active compounds indicates an extra target of therapeutic drug monitoring. Numerical data of logP values show how lipophilicity changes through metabolism to facilitate excretion. The example of phenacetin - paracetamol opened up a way for improving pharmacological effect by the use of a metabolite. This review gives a detailed description of these drugs, their active and major metabolites found in humans or animals, metabolizing cytochrome P450s, and the most recent analytical methods for their determination.

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.

The impact of educating parents of leukemic children on the patients' quality of life.

BACKGROUND: The quality of life of children with leukemia is reduced by fear and anxiety of parents after diagnosis, lack of information about the disease, treatments, and care of the child. This study aims to evaluate the effect of educating parents of leukemic children on the patients' quality of life. METHODS: In this interventional study, sixty parents of ALL children who met inclusion criteria were selected using simple random sampling method, and assigned to the experimental and control groups. The study tool included a valid and reliable questionnaire (TNO-AZL), that was filled in through interview by parents before and two months after the intervention for both groups. The first part of the questionnaire included demographic items and the second part (7 dimensions, each with 8 sections) contained questions related to the quality of life. The scores could range between 56 and 280 and a higher score represented a better quality of life. The intervention included three one-hour classes composed of lecture and question-answer sessions which were held for groups of 4-6 participants, accompanied by a booklet. RESULTS: Before the intervention, the quality of life score in the experimental and control groups was 180.83±14.43 and 174.28±20.72, respectively; after the intervention, these figures changed to 226.9±11.76 and 174.41±20.42 respectively. Paired samples T-test proved a significant increase in the quality of life in the experimental group. CONCLUSION: Parent education successfully increased the quality of life of leukemic children; therefore, parental consultation sessions and educational programs are recommended.

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.

Tuberculous osteomyelitis of the long bones and joints.

Skeletal tuberculosis(TB) is usually a rare osteoarticular disease in which bones or joints are involved. We studied 4 such cases admitted to Iranian National Research Institute of Tuberculosis and Lung Diseases from 2000 to 2003. In the initial stages of the disease, diagnosis is very difficult and conventional radiographies often reveal nonspecific findings. Our experience in these cases showed that a high index of suspicion is the most important step in early diagnosis of skeletal tuberculosis.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors.

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996-2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17-53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.