In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications.

Background

Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.

Methods

The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.

Results

The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.

Conclusions

In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

In spite of the extreme rise to the knowledge of nanotechnology in pharmaceutical sciences, there are currently limited experimental works studying the interactions between nanoparticles (NPs) and the biological system. Adjustment of size and surface area plays the main role in the reaction between NPs and cells leading to their increased entrance into cells through skin, gastrointestinal and respiratory system. Moreover, change in physicochemical reactivity of NPs causes them to interact with circulatory and cellular proteins differentially leading to the altered parameters of their biokinetics, including adsorption, distribution, translocation, transformation, and elimination. A direct relationship between the surface area, reactive oxygen species generating capability, and proinflammatory effects of NPs have been found in respiratory tract toxicity. Additionally, complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanodrugs have been well defined. Inhalation studies of some NPs have confirmed the translocation of inhaled materials to extra pulmonary organs such as central nervous system (CNS) via olfactory neurons and induction of inflammatory response. Injectable uncoated NPs have a tendency to remain on the injection site while the poly ethanol glycol (PEG)-coated NPs can be notably drained from the injection site to get as far as the lymph nodes where they accumulate. This confirms the existence of channels within the extracellular matrix for NPs to move along. Furthermore, induction of DNA strand breaks and formation of micronuclei have been recorded for exposure to some NPs such as single-walled carbon nanotubes.

In the recent years, most of the studies have simply outlined better efficacy of nanodrugs, but few discussed their possible toxic reactions specially if used chronically. Therefore, we emphasize that this part of the nanoscience must not be undermined and toxicologists must be sensitive to set up suitable in vivo or in vitro toxicity models. A system for collecting data about the relationships between NPs’ structure-size-efficacy-toxicity (SSET) should be specified with special regard to portal of entry and target organ.

Sulfur mustard is an alkylating substance still regarded as a threat in chemical warfare and terrorism. Lung parenchymal damage occurs in the most severe inhalational exposures. It accompanies an increased risk of respiratory tract carcinomas and chronic respiratory sequelae including chronic bronchitis, bronchiectasis, pulmonary fibrosis, interstitial lung disease, emphysema, and bronchiolitis obliterans. Pirfenidone is an antifibrotic with anti-inflammatory and anti hydroxyl radical activities which stabilizes pulmonary function in idiopathic pulmonary fibrosis patients. It can be suggested in chronically exposed soldiers or workers with signs and symptoms of pulmonary fibrosis to improve their quality of life and even prognosis.

Background

A specific and sensitive UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of curcuminoids. These Curcuminoids comprises of curcumin, a principal curcuminoid and other two namely, demethoxycurcumin, and bisdemethoxycurcumin obtained from rhizomes of Curcuma longa an ancient Indian curry spice turmeric, family (Zingiberaceae).

Methods

These analytes were separated on a reverse phase C18 column by using a mobile phase of acetonitrile: 5% acetonitrile in water with 0.07% acetic acid (75:25 v/v), flow rate of 100 μL/min was maintained. The qTOF-MS was operated under multiple reaction monitoring (MRM) mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions in the positive mode for curcuminoids were at m/z 369.1066, 339.1023 and 309.0214 respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique.

Results

The total run time was 5 min and the peaks of the compounds, bisdemethoxycurcumin, demethoxycurcumin and curcumin occurred at 2.06, 2.23 and 2.40 min respectively. The calibration curves of bisdemethoxycurcumin, demethoxycurcumin and curcumin were linear over the concentration range of 2–1000 ng/mL (r2, 0.9951), 2–1000 ng/mL (r2, 0.9970) and 2-1000 ng/mL (r2, 0.9906) respectively.

Intra-assay and inter-assay accuracy in terms of % bias for curcumin was in between −7.95to +6.21, and −7.03 to + 6.34; for demethoxycurcumin was −6.72 to +6.34, and −7.86 to +6.74 and for bisdesmetoxycurcumin was −8.23 to +6.37 and −8.47 to +7.81. The lower limit of quantitation for curcumin, demethoxycurcumin and bisdemethoxycurcumin was 2.0 ng/mL. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). This validated method was used during pharmacokinetic studies of curcumin in the mouse plasma.

Conclusions

A specific, accurate and precise UPLC-qTOF-MS/MS method for the determination of curcumin, demethoxycurcumin and bisdemethoxycurcumin both individually and simultaneously was optimized.

Background and the purpose of the study

Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels.

Methods

Ter-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA) were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism.

Results and major conclusion

Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n) derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1) showing swelling controlled mechanism. The mechanical strength and controlled release capability of the systems indicate that these co-polymeric hydrogels have a great potential to be used as colon drug delivery device through oral administration.

Background

Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI).

Methods

As a randomized clinical trial, one hundred twenty patients (103 male and 17 female) with angiographically confirmed CAD who were on long-term beta blocker therapy (≥3 months) enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60) in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60) without discontinuation of beta-blockers prior to DMPI.

Results

No significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility) in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096). Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001); however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898). The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7%) was not statistically different from group B (90%).

Conclusion

Beta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.

Background

Metformin an oral hypoglycemic has been widely used as a fist line of treatment of Type II Diabetes but in a very high dose 2–3 times a day and moreover suffers from a number of side effects like lactic acidosis, gastric discomfort, chest pain, allergic reactions being some of them. The present work was conducted with the aim of sustaining the release of metformin so as to decrease its side effects and also reduce its dosing frequency using a novel delivery system niosomes (non-ionic surfactant vesicles). Non-ionic surfactant vesicles of different surfactants were prepared using thin film hydration technique and were investigated for morphology, entrapment, in-vitro release, TEM (transmission electron microscopy) and physical stability. Optimized formulation was further studied for the effect of Surfactant concentration, DCP (Dicetyl phosphate), Surfactant: cholesterol ratio and volume of hydration. The release studies data was subjected to release kinetics models.

Results

The prepared vesicles were uniform and spherical in size. Optimized formulation MN3 entrapped the drug with 84.50±0.184 efficiency in the vesicles of the size 487.60±2.646 and showed the most sustained release of 73.89±0.126. Also it was resulted that 100 molar concentration of cholesterol and surfactant, Presence of DCP, equimolar ratio of span 60: cholesterol and 15 ml of volume of hydration were found to be optimum for miosome preparation.

Conclusions

The present work concluded metformin loaded niosomes to be effective in sustaining the drug release leading to decreased side effects and increased patient compliance.

Background and purpose of the study

The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination.

Methods

Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed.

Results

The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used.

Conclusion

It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.

Background

There are some reports on the effects of antidepressants on metabolic syndrome. However, our search in the previously published literature showed a lack of information on the comparison of the effects of different classes of antidepressants on lipid profile. Therefore, this study was aimed to compare the effects of fluoxetine and imipramine on serum total cholesterol (TC) and triglyceride (TG) as well as body weight (BW) in patients with major depressive disorder.

Methods

Fifty one patients, 18 to 70 years of age, with major depressive disorder complied with the criteria of this preliminary, open-label clinical trial. Subjects received either imipramine (75–200 mg/day) or fluoxetine (20–40 mg/day) for 8 weeks. Total cholesterol and TG levels, as well as BW were compared at baseline with those at weeks 4 and 8. Data was analyzed by SPSS software version 16.0.

Results

In the fluoxetine group, TC levels decreased from 165.71 mg/dL to 156.71 mg/dL at week 4 (P = 0.07), and to 143.94 mg/dL at week 8 (P = 0.16); TG levels decreased from 129.35 mg/dL to 115.88 mg/dL at week 4 (P <0.001), and to 110.41 mg/dL at week 8 (P = 0.56). In the imipramine group, TC levels increased from 169.10 mg/dL to 178.69 mg/dL at week 4 (P = 0.07), and to 208.69 mg/dL at week 8 (P < 0.001) while TG levels increased from 111.73 mg/dL to 128.83 mg/dL at week 4 (P = 0.005), and to 160.90 mg/dL at week 8 (P < 0.001). BW was significantly increased in the imipramine group at weeks 4 and 8. In the fluoxetine group, BW was non-significantly decreased from 75.69 ± 7.97 Kg (baseline) to 75.67 ± 8.01 Kg at week 4 (P = 0.88), and to 75.22 ± 8.67 Kg at week 8 (P = 0.20), while in the imipramine group, BW had significant increases from 72.53 ± 8.55 Kg (baseline) to 73.95 ± 8.61 mg/dL at week 4 (P < 0.001), and to 75.13 ± 8.34 mg/dL at week 8 (P < 0.001).

Repeated measures ANOVA showed significant effects on both TC and TG levels as well as on BW in all patients receiving imipramine. However, in patients on fluoxetine, repeated measures ANOVA showed significant effects of this medication only on TC levels in males.

Conclusions

Monitoring TC and TG and BW is recommended before starting imipramine in depressed patients with increased risk for cardiovascular disease. Fluoxetine may be the preferred agent in those with high or borderline high lipid levels.

Background

A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.

Results

Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM).

Discussion

The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

Background and the purpose of this study

Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. In vitro and in vivo studies suggest that certain polysaccharides affect immune system function. Morchella conica (M. conica) is a species of rare edible mushroom whose multiple medicinal functions have been proven. Thus, the objective of this study is to isolate and characterize of exopolysaccharide from submerged mycelial culture of M. conica, and to evaluate its immunomodulatory activity.

Methods

A water-soluble Morchella conica Polysaccharides (MCP) were extracted and isolated from the fermentation broth of M. conica through a combination of DEAE-cellulose and Sephacryl S-300 HR chromatograph. NMR and IR spectroscopy has played a developing role in identification of polysaccharide with different structure and composition from fungal and plant sources, as well as complex glycosaminoglycans of animal origin. Thus, NMR and IR spectroscopy were used to analyze the chemical structure and composition of the isolated polysaccharide. Moreover, the polysaccharide was tested for its immunomodulatory activity at different concentrations using in vitro model.

Results

The results showed that MCP may significantly modulate nitric oxide production in macrophages, and promote splenocytes proliferation. Analysis from HPLC, infrared spectra and nuclear magnetic resonance spectroscopy showed that MCP was a homogeneous mannan with an average molecular weight of approximately 81.2 kDa. The glycosidic bond links is →6)-α-D-Man p-(1→.

Conclusion

The results suggested that the extracted MCP may modulate nitric oxide production in macrophages and promote splenocytes proliferation, and it may act as a potent immunomodulatory agent.

Background

Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata.

Methods

The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection in immunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazole and itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns of the organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI). The potential gene(s) implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP). Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s) in resistant isolates as compared to sensitive and reference strains.

Results and conclusions

The aldo-keto-reductase superfamily (AKR gene) was upregulated in the resistant clinical isolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.

Background and the purpose of the study

Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative.

Methods

4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme.

Results

It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM).

Conclusion

The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.

Background

The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.

To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS).

Method

By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed.

Results

After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07).

Conclusion

Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.

Background and the purpose of the study

Natural products from plants have an important role in the development and production of new drugs mainly for cancer therapy. More recently, we have shown that the pericarp methanolic extract of Pistacia atlantica sub kurdica (with local name of Baneh) as a rich source of active biological components with high antioxidant and radical scavenging activities, has ability to cease proliferation and induce apoptosis in T47D human breast cancer cells. The present study aimed to clarify whether Baneh extract able to alter cell cycle progression of T47D cells or not.

Methods

In order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively.

Results

Baneh extract induced G0/G1 cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G2/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance.

Conclusion

Taken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.

Background

A series of 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives were synthesized and evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.

Methods

The one-pot, three-component reaction of α or β-naphthol, malonitrile and an aromatic aldehyde in the presence of diammonium hydrogen phosphate was afforded the corresponding 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives, All target compounds were evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.

Results

Among all tested compounds, unsubstituted 4-phenyl analog 4a showed Src kinas inhibitory effect with IC50 value of 28.1 μM and was the most potent compound in this series. In general, the compounds were moderately active against BT-20. 3-Nitro-phenyl 4e and 3-pyridinyl 4h derivatives inhibited the cell proliferation of BT-20 cells by 33% and 31.5%, respectively, and found to be more potent compared to doxorubicin (25% inhibition of cell growth).

Conclusion

The data indicate that 4-aryl-4H-naphthopyrans scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

Background and purpose of the study

Recent studies demonstrate that androgens, beyond regulating sexual behavior, exert several neuroprotective functions in the brain. The present study was designed to explore effect of testosterone in memory impairment induced by intra- cerebroventricular (icv) injection of streptozotocin (STZ) as a model of sporadic AD.

Methods

Study was carried out on male Wistar rats. Animals were randomly divided into 11 equal groups. Experimental model of AD was induced by bilateral icv injection of STZ at the dose of 750 μg/Rat/10 μl ACSF at days 1 and 3. STZ-induced memory impairment was assessed two weeks after the last dose of STZ by using a passive avoidance task (1 mA). The interval between the placement of animals in the illuminated chamber and the entry into the dark chamber was measured as a step-through latency (STL). Castration was performed by surgical removing of testis and behavioral study of memory impairment was done after 4 weeks.

Results

Results of this study showed that icv injection of STZ could induce marked (p < 0.05) memory impairment at the dose of 750 μg/Rat/dissolve10 μl CSF/bilateral/days 1 and 3. Therefore, we used this dose of STZ for induction of experimental model of AD. Memory was worsened in castrated rats (P < 0.05) when compared with normal and sham-operated animals. Testosterone replacement therapy (1 mg/kg, sc, for 6 days) in 4 week castrated rats restored memory up to the level of control groups. Testosterone had not any significant effect on memory impairments of non-castrated rats.

Major conclusion

According to the obtained results it can be concluded that testosterone improves cognitive and memory impairment of AD. We suggest that testosterone replacement therapy may have beneficial effect in ameliorating memory impairments of senile patients suffering from AD. Further clinical studies should be carried out to prove possible useful effect of testosterone as an adjuvant therapy in AD.

Background

Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea.

Methods

A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day) for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks), the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no) of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study.

Results

The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001). The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001). No notable complication or side effect was reported in relation to Mentha longifolia L. syrup.

Conclusion

In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea.