Pharmacological Active Substances Research Articles

Halogenation of Pharmaceuticals Is an Impediment to Ready Biodegradability

For pharmacological reasons many active organic pharmaceutical substances (AOPSs) are singly or multiply halogenated. Halogenation can confer optimised steric fitting of an AOPS to its molecular receptor; moreover, by increasing the lipophilicity of a compound, passive permeation through bilipid membranes into target cells is enhanced. As halogenation is widely suspected to inhibit biodegradability in wastewater treatment plants, the relationship of halogenation vs. ready biodegradability was investigated. Among 230 AOPSs with empirical ready biodegradability data, all 70 halogenated AOPSs are not readily biodegradable, and halogenation is confirmed to be an impediment to ready biodegradability. As a counterexample to halogenation, hydrophilic substitutions (hydroxy, carboxylic-acid or terminal-amine groups) are positively correlated with ready biodegradability. Regarding halogenation, therefore, pharmacological goals stand in stark contrast to environmental goals. Possible ideas toward solutions for this contradiction are discussed.

Fusu mixture alleviates inflammatory reactions in lipopolysaccharide-induced acute respiratory distress syndrome mice via regulation of surfactant-associated protein C, aquaporin 5, and Notch1.

Acute respiratory distress syndrome (ARDS) is a common life-threatening critical illness with high mortality. Fusu mixture (FSM) can improve the mechanical ventilation in ARDS patients. However, the detailed pharmacological mechanisms and active substances of FSM are still unclear. This study aimed to explore the potential pharmacological mechanisms of FSM for treating ARDS and its chemical compositions. A lipopolysaccharide (LPS)-induced ARDS mouse model was established, and the mice subsequently received FSM (50 mg/kg) orally for 5 days. Then, the blood samples and lung tissues were collected. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum, and histopathology examinations were applied to analyze the inflammatory response of lung tissues in ARDS mice. In addition, protein expressions of aquaporin 5 (AQP-5), surfactant-associated protein C (SP-C), and Notch1 were detected by western blot assays and immunohistochemical (IHC) examination. In addition, the chemical compositions of FSM were analyzed by high performance liquid chromatography (HPLC), using standard reference agents. After LPS induction, the serum levels of IL-6 and TNF-α in ARDS mice were significantly increased (P<0.01, vs. Control), and FSM significantly reduced these 2 pro-inflammatory cytokines (IL-6 and TNF-α) compared to the model mice (P<0.01). Histopathology examinations showed FSM significantly attenuated the inflammatory responses in lung tissues. Furthermore, after FSM treatment, the SP-C and AQP-5 were significantly increased, compared to the Model mice (P<0.01), and FSM also up-regulated the Notch1 expressions in lung tissues of ARDS mice (P<0.001, vs. Model). Collectively, it is suggested that FSM alleviates inflammatory reactions and promotes the proliferation of alveolar epithelial cells in LPS-induced ARDS mice via regulation of SP-C, AQP-5, and Notch1 in lung tissues.

Occurrence and ecotoxicological risk assessment of pharmacologically active dyes in the environmental water of Poland

The interest in the fate of pharmacologically active substances (PASs) in the aquatic environment continually increases. However, little is known about pharmacologically active dyes (PADs) as contaminants of water bodies.PADs are used in medicine, but due to their colouring properties are also applied in the textile, cosmetic and food industries. Their large-scale production and widespread applications have caused these dyes permeate to the aquatic environment. The pharmacological activity and toxicological properties of some of these dyes, caused their occurrence in water should be monitored.Up to now, PADs such as crystal violet, malachite green, methylene blue, rhodamine B, have been determined in the water of Greater China and Iran. However, there is no data on whether PADs pose an environmental problem for water bodies in Poland. Thus, different water samples were collected and analysed by the UPLC-MS/MS method allowing the determination of 20 PADs. The tests showed that dyes such as crystal violet, methyl violet 2 B and rhodamine B were found in 2 out of 36 water reservoirs (0.0122–0.0594 μgL−1). The environmental risk assessment indicated that determined dyes for most model organisms did not pose a risk. Only the presence of methyl violet 2 B (0.0571 μgL−1) was related to a low risk for rohu carp, and crystal violet (0.0122–0.0209 μgL−1) showed a moderate risk for medaka fish.The occurrence of PADs was tested on a larger scale in the water samples collected from different water reservoirs in Poland. Based on obtained results, 96.3% of water samples collected from different water bodies (94.5%) were free from dyes. Thus, it could be stated that generally environmental water of Poland is contaminated with PADs at a low level. On the other hand, the presence of dyes in two samples indicates that PADs permeate the water environment, and their occurrence should be monitored.

Quantification of twenty pharmacologically active dyes in water samples using UPLC-MS/MS

This study presents a multi-compound method for the determination of 20 pharmacologically active dyes from 5 different chemical classes in environmental water samples. These compounds, including triphenylmethane dyes (malachite green, crystal violet, brilliant green, ethyl violet, methyl violet 2B, pararosaniline, victoria blue B, victoria blue R, victoria pure blue BO), phenothiazine dyes (methylene blue, azure A, azure B, azure C, new methylene blue, thionine), phenoxazine dye (nile blue A), acridine dyes (acriflavine, proflavine) and xanthene dyes (rhodamine B, rhodamine 6G) constitute pharmacologically active substances (PASs). For the optimisation of sample preparation, different solid-phase extraction (SPE) sorbents and a wide range of pH (from 2 to 12) of water samples were tested. Finally, water samples were preconcentrated and cleaned up on diol SPE cartridges. Extracts were analysed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) operating in the positive electrospray ionisation (ESI+) mode. The chromatographic separation of the 20 pharmacologically active dyes was achieved within 5 min by using a pentafluorophenyl (F5) analytical column and mobile phases of ammonium acetate buffer (0.05 M, pH = 3.5) and acetonitrile with gradient elution. The developed method was validated proving to be suitable for the determination of all tested compounds. Limits of quantification were 0.01–0.1 μg/l, are sensitive enough to quantify very low concentration levels of the dyes in environmental water samples. The obtained recovery values for all tested analytes were between 71.2 and 104.9% with a good RSD, less than 14 % at all fortification levels. The application of the developed method to water samples allows the detection of dyes such as crystal violet, rhodamine B, and methyl violet in two wastewater samples in concentration range from 0.017 to 0.0043 μg/l).

Gold Nanoparticle-Based Photo-Cross-Linking Strategy for Cellular Target Identification of Supercomplex Molecular Systems.

Cellular target identification plays an essential role in innovative drug development and pharmacological mechanism elucidation. However, very few practical experimental methodologies have been developed for identifying target proteins for supercomplex molecular systems such as biologically active phytochemicals or pharmaceutical compositions. To overcome this limitation, we synthesized gold nanoparticles (AuNPs) as solid scaffolds, which were bound with 4,4'-dihydroxybenzophenone (DHBP) as a photo-cross-linking group on the surface. Then, DHBP-modified AuNPs cross-linked various organic compounds from phytochemicals under ultraviolet radiation via carbene reactions, H-C bond insertion, for catalytic C-C bond formation. We next used the phytochemical-cross-linked AuNPs (phytoAuNPs) to pull down potential binding proteins from brain tissue lysate and identified 13 neuroprotective targets by mass spectrometry analysis. As an exemplary study, we selected Hsp60 as a crucial cellular target to further screen 14 target-binding compounds from phytochemicals through surface plasmon resonance (SPR) analysis, followed by Hsp60 activity detection and neuroprotective effect assay in cells. Collectively, this gold nanoparticle-based photo-cross-linking strategy can serve as a useful platform for discovering novel cellular targets for supercomplex molecular systems and help to explore pharmacological mechanisms and active substances.

Classification of diterpenoid alkaloids from Aconitum kusnezoffii Reichb. by liquid chromatography-tandem mass spectrometry-based on molecular networking.

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups (N1-N33). Based on the excremental fragmentation pathway of known diterpenoid alkaloids (1-9) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.

Investigation on the uptake of ciprofloxacin, chloramphenicol and praziquantel by button mushrooms

Button mushrooms are widely produced edible basidiomycetes. Commercially, they are cultivated on substrates containing fermented horse manure and chicken feces. Since pharmacologically active substances (PAS) might be introduced into the food chain via animal treatment, their residues may be present in manure used for mushroom growth. Previous studies in plants have demonstrated an uptake of PAS from the agricultural environment. The present study was performed to investigate the presence of PAS in button mushrooms. For analysis, a multi-analyte method for the detection of 21 selected PAS using liquid chromatography tandem-mass spectrometry was developed, successfully validated and applied to commercially available button mushrooms. Traces of chloramphenicol were detected in two of 20 samples. Additionally, in a mushroom cultivation experiment an uptake of ciprofloxacin, chloramphenicol and praziquantel was conducted. Throughout the whole experiment, praziquantel was present in quantifiable amounts in mushrooms and in high quantities in soil.

Chemical analysis and bioactivity evaluation of the stem of Rheum tanguticum

Rhubarb (Dahuang in Chinese), belongs to the family Polygonaceae, genus Rheum, has been employed as a traditional Chinese medicinal material for a long time. Rheum officinale, R. palmatum, R. tanguticum, R. rhaponticum, R. ribes, R. franzenbachii, and R. rhabarbarum have been reported to possess many pharmacological active substances that are used to treat diseases. The petioles of R. rhabarbarum, R. ribes, R. rhaponticum are well-known vegetables in some regions of the world. Based on this folk application and active ingredients that may be present in stems, the present study was conducted to analyze the content of nutritional components and active secondary metabolism components, and evaluate the antimicrobial activity and antioxidant activity with prepared solvent extracts. Methods published by the Association of Official Analytical Chemistry (AOAC) was used to determine the total protein, crude fat, crude fiber, vitamin C, ash, and moisture contents. The results showed that the inflorescence stem of R. tanguticum contained a higher content of crude fiber (89.14%) and vitamin C (16.96%). The content of total protein and crude fat was 8.49% and 1.34% respectively. The results showed that the DPPH Radical Scavenging Activity of the extract had a concentration-dependent effect. The highest activity (83.4%) of the methanol extract sample was recorded at 1.0 mg/mL and the lowest activity, 15.56%, was recorded at 0.2 mg/mL. 0.485 mg/mL was needed to achieve a 50% toxicity. The flavonoid and total phenolic contents of the inflorescence stem of R. tanguticum were found to be 0.022 mg/g and 4.138 mg/g respectively. A concentration of 10 mg/mL successfully inhibited the growth of the pathogenic microorganisms, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis using the paper disc diffusion method. In summary, the results of this study confirm that the inflorescence stem of R. tanguticum contains some rich nutritional components and bioactive secondary metabolism components that are beneficial for human health as edible parts or processed products. The results of bioactivity evaluation in this study also showed that the inflorescence stem of R. tanguticum could be developed natural antioxidant and antibacterial agent as a potential resource. This may possibly provide a feasible solution for non-medicinal parts utilization.

The study of neuroprotective effects and underlying mechanism of Naoshuantong capsule on ischemia stroke mice

BackgroundNaoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects.MethodsTo more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice.ResultsThe results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β-elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.ConclusionsThe present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.

A health risk for consumers: the presence of adulterated food supplements in the Netherlands

ABSTRACTThe use of food supplements is increasing. They are marketed as beneficial for health, well-being, physical or mental condition and performance, or to prevent diseases. Producers add synthetic compounds or illicit herbal material to food supplements to claim desired effects. Claims made to support marketing without scientific evidence are, however, illegal. Intake of adulterated food supplements may lead to serious adverse effects. The aim of this paper is to report the results of analyses of (adulterated) food supplements conducted by the Netherlands Food and Consumer Product Safety Authority between October 2013 and October 2018. In total, 416 supplements were analysed of which 264 (64%) contained one or more pharmacological active substances or plant toxins, such as caffeine, synephrine, sildenafil, icariin, sibutramine, higenamine, hordenine, phenethylamine, methylsynephrine, DMAA, phenolphthalein, octopamine and ephedrine. When compared to dose levels that are considered safe, daily doses of the substances in the food supplements were sometimes much higher, causing a risk for consumers who are unaware of the presence of these pharmacologically active substances. In many cases, neither food nor medicines legislation (easily) enables enforcement actions. This means that some products containing pharmacologically active substances (i.e. synthetic medicines and their illicit analogues), stay available on the market. An undesirable situation because for many of these substances no detailed toxicity data are available.

On problems and algorithm of prescribing combined medicinal preparations, containing small quantities of narcotic drugs and psychotropic substances

Aim. To analyze the regulating documents and work out the algorithm of prescribing combined medicinal preparations, containing small quantities of narcotic drugs, psychotropic substances, their precursors and other pharmacological active substances.&#x0D; Materials and methods. The normative documents, regulating the order of prescribing and selling combined medicinal preparations, containing narcotic drugs, psychotropic substances and their precursors were analyzed.&#x0D; Results. Some normative documents to regulate the order of prescribing combined medicinal preparations, containing narcotic drugs and psychotropic substances, present problems. To simplify the procedure of prescribing such medicinal preparations, there was suggested an algorithm, explaining: the choice of prescription form; conditions of prescribing combined medicinal preparation by trade name; terms of prescription validity and possibilities of their prolongation; regulated possibilities for exceeding norms of prescribing medicinal preparations and order of their registration.&#x0D; Conclusions. The suggested algorithm of the order of prescription will promote observation of requirements of the existing normative acts.

Super Antibiotics: Part III. Hyperforin, Revision of the Relative and Absolute Stereochemistry Presented by Bystrov &amp;lt;i&amp;gt;et al&amp;lt;/i&amp;gt;.

Hyperforin is an antibiotic, antibacterial, antiprotozoal, antiviral, anticancer, and immunomodulatory substance. It is possibly a new and potent tool for curative treatment of a broad array of infection diseases. Despite the medical usefulness of Hypericum perforatum L., which has been known since ancient times, its constituents were not well studied until the middle of the 20th century. Several pharmacological active substances (PASs) were then discovered as constituents of H. perforatum. Among these was the antibacterial substance, hyperforin. The chemistry and relative and absolute stereochemistry of hyperforin were studied at the Shemyakin Institute of Bioorganic Chemistry, USSR Academy of Sciences, Moscow, USSR, the Institute of Biochemistry and Physiology of Microorganisms, USSR Academy of Sciences, Moscow, USSR, and the Zabolotny Institute of Microbiology and Virology at the Ukrainian Academy of Sciences, Kiev, UkrSSR. In this paper, hyperforin’s relative and absolute stereochemistry, as reported in earlier published former USSR literature (cited herein), is discussed, as well as cited up to date in international literature. In 1979, the relative and absolute stereochemistry of hyperforin and some constituents of H. perforatum were studied at the University of Oslo, Oslo, Norway. In 1979, Brondz et al. challenged the correctness of the relative and absolute stereochemistry of hyperforin reported previously by Bystrov et al. The relative stereochemistry of a drug is the basis for possible partial or total synthesis and absolute stereochemistry is crucial for the action of drugs on enzymes. Correct molecular isometry (absolute stereochemistry) is key for high pharmacological activity versus harm/toxicity. Elucidation of the ste-reochemistry of an unknown molecule is of great academic and theoretical interest, and in the case of a drug, it also has great practical interest.

Effect of β-cyclodextrins based nanosponges on the solubility of lipophilic pharmacological active substances (repaglinide)

Cyclodextrin based nanosponges (CD-NS) are nanostructured cross-linked polymers, usually obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole, organic carbonates or (±) epichlorohydrin. They have been used to increase the solubility and stability of poorly soluble pharmacological active substances, as they combine the complex forming properties of CDs and properties of polymers (such as the high molecular weight). The affinity of CDs for certain lipophilic molecules is characteristic to the polymeric nano-structured system and allows the development of specific drug delivery systems. Knowing that cyclodextrin capacity to form inclusion complexes is maintained and enhanced when the CD molecules form aggregates, cross-link together or copolymerize with other compounds, we have synthesized cyclodextrin based nanosponges (from β-cyclodextrin and sulfobutylether-β-cyclodextrin). The complexing properties of the polymers were investigated against repaglinide (a hypoglycemic agent, practically insoluble in water). Solubility studies were performed according to the method reported by Higuchi and Connors and the phase solubility diagrams were plotted. The repaglinide-nanosponges complexes were prepared, lyophilized and the resulted inclusion complexes were characterized by FT-IR and NMR. The solubility profile and the loading capacity of the cyclodextrin based polymers were also determined.

Ranachensinin: A Novel Aliphatic Tachykinin from the Skin Secretion of the Chinese Brown Frog, Rana chensinensis

Amphibian skin secretions contain a plethora of pharmacologically-active substances and represent established sources of bioactive peptides, including tachykinins. Tachykinins are one of the most widely-studied peptide families in animals and are found in neuroendocrine tissues from the lowest vertebrates to mammals. They are characterized by the presence of a highly-conserved C-terminal pentapeptide amide sequence motif (-FXGLM-amide) that also constitutes the bioactive core of the peptide. Amidation of the C-terminal methioninyl residue appears to be mandatory in the expression of biological activity. Here, we describe the isolation, characterization and molecular cloning of a novel tachykinin named ranachensinin, from the skin secretion of the Chinese brown frog, Rana chensinensis. This peptide, DDTSDRSN QFIGLM-amide, contains the classical C-terminal pentapeptide amide motif in its primary structure and an Ile (I) residue in the variable X position. A synthetic replicate of ranachensinin, synthesized by solid-phase Fmoc chemistry, was found to contract the smooth muscle of rat urinary bladder with an EC50 of 20.46 nM. However, in contrast, it was found to be of low potency in contraction of rat ileum smooth muscle with an EC50 of 2.98 µM. These data illustrate that amphibian skin secretions continue to provide novel bioactive peptides with selective effects on functional targets in mammalian tissues.

Potential involvement of the proton-coupled amino acid transporter PAT1 (SLC36A1) in the delivery of pharmaceutical agents

The proton-coupled amino acid transporter PAT1 (SLC36A1) is an intestinal carrier of L-proline, L-alanine and glycine. PAT1 has also been shown to transport pharmacologically active substances such as GABA, vigabatrin, δ-aminolevulinic acid and gaboxadol. The present review will discuss if the proton-coupled amino acid transporter PAT1 (SLC36A1) may be a relevant transporter for pharmaceutical exploitation. Research investigating this from both in vitro and in vivo perspectives will be highlighted. Furthermore we’ll review the current knowledge about the structure-translocation relationship for PAT1 and provide an overview of pharmacological active substances, which are substrates for PAT1 along with examples of formulation strategies aimed at exploiting the transport activity of PAT1.

Pharmaco-Modulations of Induced Edema and Vascular Permeability Changes by Vipera lebetina Venom: Inflammatory Mechanisms

The inflammatory response induced by Vipera lebetina venom (VLV) in the mice hind paw was evaluated by paw edema value and vascular permeability changes. The edema was produced in a dose- and time-dependent manner. This response was maximal within 2h and disappeared after 24h The minimum edema-forming dose was estimated at 0.8μg/20g body weight. Microscopic examination confirmed that VLV also induces skin structure alterations with collagen fiber dissociation and polynuclear infiltration, which is characteristic of edema formation. The induced edema with VLV (1μg/paw) could be due to the release of pharmacological active substances at the site of injection. Histamine, serotonine, and arachidonate metabolites may play important roles in the vasoactive and edematic effect of VLV since pretreatment of mice with cromoglycate, cyproheptadine, ibuprofen, loratidine, and indomethacin significantly reduced the edema formation (77, 63, 57, 45, and 43%, respectively). The obtained results demonstrate that the induced edema and vasodilatation by this venom may be triggered and maintained by different pharmacological mechanisms, since cromoglycate and cyproheptadine were the most active inhibitors of the edema. The relationships between histamine and serotonin release from mast cells and arachidonate metabolites activation could be the main step in edema-forming and the induced vasodilatation by the venom.

Evaluation of the antibacterial residue surveillance programme in Danish pigs using Bayesian methods

Residues of pharmacological active substances or their metabolites might be found in food products from food-producing animals. Maximum Residue Limits for pharmacological active substances in foodstuffs of animal origin are established to assure high food safety standards.Each year, more than 20,000 samples are analysed for the presence of antibacterial residues in Danish pigs. This corresponds to 0.1% of the size of the slaughter pig population and more than 1% of the sows slaughtered. In this study, a Bayesian model was used to evaluate the Danish surveillance system accuracy and to investigate the impact of a potential risk-based sampling approach to the residue surveillance programme in Danish slaughter pigs. Danish surveillance data from 2005 to 2009 and limited knowledge about true prevalence and test sensitivity and specificity were included in the model.According to the model, the true antibacterial residue prevalence in Danish pigs is very low in both sows (∼0.20%) and slaughter pigs (∼0.01%). Despite data constraints, the results suggest that the current screening test used in Denmark presents high sensitivity (85–99%) and very high specificity (>99%) for the most relevant antibacterial classes used in Danish pigs.If high-risk slaughter pigs could be identified by taking into account antibacterial use or meat inspection risk factors, a potential risk-based sampling approach to antibacterial residue surveillance in slaughter pigs would allow reducing the sample size substantially, while increasing or maintaining the probability of detection. Hence, the antibacterial residue surveillance programme in Danish pigs would be more cost-effective than today.

Characterization and Release Kinetics of Allylthiosufinate and its Transforments from Poly(d,l-Lactide) Microspheres

In this work was described poly(d,l-lactide) microwave synthesis using tin(II) 2-ethylhexanoate initiated ring-opening polymerization. Polymerization was performed at 100 °C with monomer to initiator molar ratio ([M]/[I]) of 5,000 in 30 min. The achieved number average molar mass of obtained polymers (determined by gel permeation chromatography) was 102,320 g/mol, with the polydispersion index, Q, 2.80. Structural characterization was performed by FT-IR spectroscopy followed characteristic bands. For applicative purposes the obtained polymer was purified during the procedure of microsphere preparation. Biodegradable microspheres prepared from poly(d,l-lactide) have been widely studied in recent years and have become well established controlled drug delivery systems. In this work microspheres were loaded with allyl thiosulfinate (allicin) and its transforments products (ajoene and vinyldithiine), as pharmacological active substances. The morphology of the microspheres was analyzed using a scanning electron microscope. Allicin was synthesized by acid oxidation of allyl disufide and purification of obtained products by liquid–liquid extraction with diethyl ether. Obtained allicin, purity 73%, was transformed using microwave in acetone solution, at solvent boiling temperature, for 5 min. For the quality and quantity analysis of allicin and its transformation process was used LC/MS chromatography. (E)- and (Z)-ajoene were detected at retention time 3.1 and 3.3 min, respectively, whence 3-vynil-4H-1,2-dithiine and 2-vynil-4H-1,3-dithiine were detected at 4.3 and 4.8 min, respectively. Retention time of allicin was 2.93 min, according to liquid chromatography results. HPLC method was used for assessment of pharmaceutical substances (alicine and alicine transforments) releasing from microspheres at room temperature in solutions with different pH (pH = 3 and pH = 8) for 24 h.

The Effect of Melatonin Treatment and Exposure to Continuous Darkness on the Reactivity of Smooth Muscles to Drugs in Rats

Melatonin is the major secretory product of the pineal gland, playing an integral role in numerous metabolic, physiological and behavioral processes.This study represents an attempt to understand the effect of environmental changes on the responses of a selected isolated tissue to pharmacologicallyactive substances in certain species which may lead to important experimental and clinical implications in future. Twenty male albino wistar rats were dividedinto three experimental groups:Group 1: Control animals, comprising 6 rats were exposed to 12:12 hour light: dark cycle for 4 weeks.Group 2: Composed of 8 rats, was kept in a dark environment for 4 weeks.Group 3: Consisted of 6 rats aged 6-7 weeks, subjected to continuous darkness for 2 weeks, at the end of the first week the rats treated daily with s.c melatonin injection at 1.00 p.m. for 7 consecutive days. The result of this study showed that the vas deferens preparation from the third group reacted with significant increase in reactivity to nor-adrenaline and 5-HT than that of control and continuous dark animals.The limitation of time and shortage of materials may be blamed for the kind and quantity of results obtained and the conclusions made. Therefore, further studies with regard to the exposure period have to be undertaken in future to extensively elaborate on this point.

Screening suspected counterfeit Viagra ® and imitations of Viagra ® with near-infrared spectroscopy

We describe a near-infrared spectroscopy (NIRS) method for fast-screening Viagra ® tablets, counterfeit Viagra tablets, and imitations of Viagra. The method can (1) check the homogeneity of a batch; (2) distinguish counterfeits and imitations from authentic Viagra ®; (3) screen for the presence of sildenafil citrate, the pharmacologically active substance in Viagra ®, irrespectively of the excipients present; (4) and detect whether similar samples have been previously analysed. We applied the method to 103 samples with a diversity of appearance, chemical composition, and origin. Other analytical methods confirmed the positive screening results for sildenafil citrate and the presence of other pharmacological active substances. The NIRS screening indicated the absence of sildenafil citrate in the presence of another pharmacological substance for only 2 samples, where the reference methods showed the presence of sildenafil citrate in addition to that of clomifene citrate. Otherwise, the method gave no false positive or negative results. The NIRS screening method is very fast and reliable for detecting counterfeits and imitations, and it correctly predicts the presence or absence of sildenafil citrate in 98% of the samples.