Breast cancer is the foremost common malignancy among the female population around the world. Female breast cancer incidence rates have increased since 1980, slowed in 1990, the rate of increase have leveled off since 2001. In spite of the advances in the early detection, treatment, surgery and radiation support, almost 70% of the patients develop metastasis and die of the disease. Around 10% of the patients when diagnosed with breast cancer have metastases. Survival among the breast cancer patients have increased due to the introduction of novel single agent, combination of chemotherapeutic agents and targeted biologic agents, which is breast cancer specific. The staging of tumor-node-metastasis is significant for the prognosis and treatment. Predominantly the combination of chemotherapeutic regimen is given to improve the rate of clinical benefit and the overall survival rate. Novel mono-therapeutic options are being used often in metastatic setting as they will not be able to endure the toxicity of the combination regimen. Usually, endocrine therapy is recommended for hormone-responsive breast cancer due to efficacy and favorable side effect profile but chemotherapy becomes an option when endocrine therapy fails. This review summarizes the newer therapeutic options for early breast cancer and advanced breast cancer that are pretreated heavily on other chemotherapeutic agents. Further it provides monotherapies and other emerging novel combination regime which can be opted for first line or second line setting.
Breast cancer; metastasis; novel monotherapy; combination regimen; clinical benefit rate
The characterization and classification of smokeless tobacco products has been a continuously evolving process. This is based on a number of different parameters like nicotine content, moisture content, amount of heavy metals, pH, and in vitro cytotoxicity assays. Their contexts often vary between countries, research institutions, and legal requirements. The categorisation of these products is quite challenging due to the diffused sample sizes, diverse array of branded products on offer, and the absence of a centralized manufacturing facility. This study aims at a systematic classification of 10 smokeless tobacco product samples from the retail market based on their potential toxicity upon long-term use. The estimation of potential toxicity follows a well-established method that employs the concentration of toxic metals in the different samples. The potential toxicity as well as heavy metal concentrations of the smokeless tobacco products analysed was found to be much higher than acceptable limits. For instance, the levels of lead, cadmium, copper and zinc of 2.5, 1, 4 and 23 ppm, respectively, are well above their recommended limits. The results from the study indicate that chronic use of smokeless tobacco products is a significant health risk, especially in the vulnerable population. Further studies of this nature will help establish a toxicological fingerprint on the diverse class of products that floods the market now.
Smokeless tobacco products; tobacco pH; chewing tobacco; potential toxicity; trace metals
Coptidis Rhizoma (Coptis chinensis) has been reported to have antioxidative effect on hemolysis of erythrocytes induced by acetylphenylhydrazine in mice and rats. However, the ability of Coptidis Rhizoma to protect structure and function of erythrocytes membrane and morphology of erythrocytes against oxidative damage remains unknown. In this study, we undertook a characterization of antioxidative activity in erythrocytes membrane of Coptidis Rhizoma using an in vivo model of acetylphenylhydrazine-induced mice together with in vitro studies with 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced erythrocytes for further morphology characterization. Acetylphenylhydrazine-induced mice were treated intragastrically with Coptidis Rhizoma at doses of 0.3, 0.6, and 1.2 g/kg per day for 3 days and at the dose of 0.6 and 1.2 g/kg it showed that there was an increasing trend in membranes cytoskeletal proteins of band I-IV, especially a significant upregulation in band II. Significant increase in phosphatidylserine and phosphatidylcholine content at the dose of 1.2 g/kg Coptidis Rhizoma was obsereved. At all doses of Coptidis Rhizoma, the declined membrane fluidity of acetylphenylhydrazine-induced mice was significantly increased. In addition, at the dose of 1.2 g/kg Coptidis Rhizoma treatment showed a significant increase in Ca2+/Mg2+-ATPase activity and there was an increasing trend in the activity of Na+/K+-ATPase. In vitro, Coptidis Rhizoma protected erythrocytes from 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced hemolysis in a dose-dependent manner at concentrations of 0.25-1.5 mg/ml, and also significantly inhibited the 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced morphological alterations in mice erythrocytes. These results demonstrate that Coptidis Rhizoma is capable of protecting erythrocytes against oxidative damage probably by acting as an antioxidant and maintaining membrane integrity.
Coptidis rhizoma; erythrocytes membranes; hemolysis; oxidative damage
Present manuscript describes the sustained and targeted delivery of 5-aminosalicylic acid to the distal ileum and proximal colon, using dextran (40 kDa) as a carrier for targeting 5-aminosalicylic acid at the colonic site by attaching p-aminobenzoic acid and benzoic acid as linkers. Prepared conjugate were characterized by UV, HPLC, FT-IR, and 1H NMR. The degree of substitution was estimated by complete hydrolysis of conjugates in borate buffer and in vitro hydrolysis study of conjugates was performed in different biological media. It was observed that 5-aminosalicylic acid alone have produced high incidence of gastric ulcer with high ulcer index whereas lower ulcer index was found for the dextran conjugates of 5-aminosalicylic acid. The release pattern of conjugates in 3% w/v rat caecal content was confirmed the colon specificity of 5-aminosalicylic acid conjugates.
5-ASA; dextran; colon-specific; ulcerogenic study
A simple, specific, accurate, and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of montelukast and fexofenadine hydrochloride, using a Lichrospher® 100, RP-18e column and a mobile phase composed of methanol:0.1% o-phosphoric acid (90:10 v/v), pH 6.8. The retention times of montelukast and fexofenadine hydrochloride were found to be 10.16 and 12.03 min, respectively. Linearity was established for montelukast and fexofenadine hydrochloride in the range of 2-10 μg/ml and 24-120 μg/ml, respectively. The percentage recoveries of montelukast and fexofenadine hydrochloride were found to be in the range of 99.09 and 99.81%, respectively. Both the drugs were subjected to acid and base hydrolysis, oxidation, photolytic, and thermal degradation conditions. The degradation products of montelukast and fexofenadine hydrochloride were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of montelukast and fexofenadine hydrochloride in bulk drugs and formulations.
Montelukast; fexofenadine hydrochloride; degradation products; stability-indicating method; HPLC
The aim of this study was to enhance the dissolution rate of efavirenz using solid dispersion systems (binary and ternary). A comparison between solvent and fusion method was also investigated. Solid dispersions of efavirenz were prepared using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of both. Tween 80 was incorporated to obtain a ternary solid dispersion system. Dissolution tests were conducted and evaluated on the basis of cumulative percentage drug release and dissolution efficiency. Physicochemical characterizations of the solid dispersions were carried out using differential scanning calorimetric, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Dissolution was remarkably improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10 formulations formed using solvent method showed further improvement in the dissolution rate. Physicochemical characterization results suggested that efavirenz existed in the amorphous form in all the solid dispersion systems providing evidence of improvement in dissolution. No statistically significant difference (P>0.05) in dissolution was observed between the two methods. Binary and ternary solid dispersion systems both have showed a significant improvement in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone K30 showed best dissolution profile and 1:10 was identified as an optimum drug-polymer weight ratio.
Solid dispersion; efavirenz; dissolution enhancement; polyethylene glycol; PVP K30; Tween 80
The objective of our work was to study the micromeritic properties of lyophilized diclofenac potassium-loaded lipospheres and to evaluate in vivo, the analgesic properties of diclofenac potassium in the lipospheres in addition to other in vitro properties. Solidified reverse micellar solutions were prepared by fusion using 1:1, 2:1, and 1:2% w/w of Phospholipon® 90H and Softisan® 154. Diclofenac potassium (1, 3, and 5% w/w) was incorporated into the solidified reverse micellar solutions. Solidified reverse micellar solutions-based lipospheres were formulated by melt homogenization techniques using Ultra-Turrax homogenizer, and thereafter lyophilized to obtain water-free lipospheres. The lipospheres were characterized in terms of particle size and morphology, stability, thermal analysis, drug content, encapsulation efficiency, and loading capacity. The flow properties of the lipospheres were studied using both direct and indirect methods of assessing flow. The analgesic properties of the lipospheres were studied using the hot plate method. Results obtained showed that the yield of diclofenac potassium-loaded lipospheres was high and the particle size ranged from 0.61±0.07 to 2.55±0.04 μm. The lipospheres had high encapsulation efficiency of 95%, which was affected by the amount of drug loaded, while the loading capacity increased with the increase in drug loading. Diclofenac potassium-loaded lipospheres exhibited poor flow. The formulations exhibited good analgesic effect compared with the reference and had 84 to 86% drug release at 13 h. The lipospheres based on solidified reverse micellar solutions could be used for oral delivery of diclofenac potassium.
Solidified reverse micellar solution; lipospheres; micromeritics; diclofenac potassium; analgesic
A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have been synthesized in good yields and structures of these compounds were established by IR, 1H NMR, 13C NMR, mass spectral, and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by the broth dilution assay method. Twenty one of these compounds displayed good antimicrobial activity, with a MIC value of 1-4 μg/ml. Several compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular activity with MIC value 1-2 μg/ml. Further, some title compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit antitubercular activity at non-cytotoxic concentrations.
Pyrroles; acid hydrazide derivatives; antibacterial activity; antitubercular activity; antifungal activity; broth dilution assay method; cytotoxicity
Picrorhiza kurroa is a well-known herb in Ayurvedic medicine. Although it shows antioxidant, antiinflammatory and immunomodulatory activities, it is most valued for its hepatoprotective effect. The rhizomes are widely used against indigestion problems since ancient times due to improper digestive secretions. Aim of this study was to explore antioxidant study of P. kurroa leaves for a new source of naturally occurring antioxidants. Two pure compounds, luteolin-5-O-glucopyranoside (1) and picein (2) were isolated from butanol extract through column chromatography. Different extracts of P. kurroa leaves (ethanol, ethyl acetate, butanol) were quantified for isolated compound (2) by high-performance liquid chromatography. All the extracts and isolated compounds were evaluated for its antioxidant activity using two assays, 2,2-diphenyl-1-picrylhydrazyl radical and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assay. The linear detection range was 1.56-200 μg/ml for picein. The limit of detection and limit of quantification for picein were 2.34 and 7.81 μg/ml, respectively. Butanol and ethyl acetate extract showed greater antioxidant activity as compare to ethanol extract. Compound 1 and ascorbic acid showed nearly similar antioxidant activity where as 2 showed no activity at standard concentration. The IC50 values for 2,2-diphenyl-1-picrylhydrazyl radical and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assay for ascorbic acid, compound 1, ethanol extract and its different fractions (ethyl acetate and butanol) were found to be 0.81, 1.04, 67.48, 39.58, 37.12 and 2.59, 4.02, 48.36, 33.24, 29.48 μg, respectively.
Picrorhiza kurroa; leaves; HPLC; antioxidant activity; DPPH; ABTS
A new, sensitive and selective high-performance liquid chromatography–tandem mass spectrometric method has been developed for the determination of six major flavonoids including sophoricoside, genistin, genistein, rutin, quercetin, kaempferol in Fructus sophorae. Principal component analysis and hierarchical clustering analysis were used to classify and differentiate these samples. Chromatographic separation was performed on a C18 column with linear gradient elution of methanol and 0.05% acetic acid (v/v) at a flow rate of 0.8 ml/min. The detection was accomplished in the negative mode using multiple-reaction monitoring. The total run time was 8.0 min. Full validation of the assay was carried out including linearity, precision, accuracy, recovery, limit of detection and limit of quantification. The validated method was successfully applied to the simultaneous determination of these active components in Fructus sophorae. The results demonstrated that the quantitative difference in content of six active compounds was useful for chemotaxonomy of many samples from different sources and the standardization and differentiation of many similar samples. Simultaneous quantification of bioactive components by high-performance liquid chromatography–tandem mass spectrometric method coupled with chemometric techniques would be a well-acceptable strategy to comprehensively control the quality of Fructus sophorae.
Flavonoids; Fructus sophorae; quantification; LC-MS/MS; principal components analysis; hierarchical clustering analysis
A novel, efficient and simple approach for soy phosphatidylcholine analysis according to its fatty acid composition was studied with reverse-phase high-performance liquid chromatography. The reverse-phase high-performance liquid chromatography analysis was performed isocratically using UV detector and simple mobile phase solvents consisting of isopropyl alcohol, methanol, and deionized water in the proportion of 70:8:22 v/v. The uniqueness of the proposed method was the separation of individual fatty acids of soy phosphatidylcholine. The high-performance liquid chromatography method for soy phosphatidylcholine was validated for linearity with correlation coefficient of above 0.99 for all the peaks separated according to their fatty acid composition. The intra-day and the inter-day precision studies provided the relative standard deviation of less than 2%. The limit of detection and limit of quantitation values were also calculated for all the resolved peaks of soy phosphatidylcholine. Also system performance parameters such as number of theoretical plates, capacity factor, tailing factor, separation factor, and peak resolution were studied systematically and found well within the acceptable range. The proposed high-performance liquid chromatography method was successfully applied to soy phosphatidylcholine extracted and purified from deoiled soy lecithin without any interference of impurities or solvent peaks. Individually, the collected peaks of sample soy phosphatidylcholine were subjected for mass spectroscopy. The mass spectra showed all the peaks having different saturated or unsaturated fatty acid chains attached to glyerophosphocholine moiety of soy phosphatidylcholine. The method developed is economic and well suited for estimation of soy phosphatidylcholine with its fatty acid composition.
Phosphatidylcholine; fatty acid; mass spectra; phospholipid; resolution
The use of metals in traditional medicines is very often seen as matter of concern these days, especially the Bhasma preparations which are always under stringent observations for containing highly reactive inorganic elements such as lead, mercury, arsenic and others. One of the Bhasma extensively used in routine Ayurvedic practice is Tamra (copper) bhasma. If it is not prepared properly or Shodhana procedure is not done properly, it acts as a poison. To indicate its toxic potential, Ashtamahadoshas (eight major ill effects) have been quoted in classics and due emphasis have been given to its Shodhana procedure. In the present study, Tamra bhasma prepared from Shodhita and Ashodhita Tamra was subjected to oral toxicity study to ascertain the role of Shodhana process on safety profile of Tamra bhasma on subchronic administration to albino rats. Both the samples were administered to rats for 45 consecutive days at the doses of 5.5, 27.5, and 55 mg/kg. Animals were sacrificed on 46th day and parameters like hematological, serum biochemical, and histopathology of various organs were studied. Results showed that Tamra bhasma prepared from Ashodhita Tamra has pathological implications on different hematological, serum biochemical and cytoarchitecture of different organs even at therapeutic dose level (5.5 mg/kg). Whereas, Tamra bhasma prepared from Shodhita Tamra is safe even at five-fold to therapeutic equivalent doses (27.5 mg/kg). These observations emphasize the role of Shodhana and importance of dose in expression of toxicity of the medicinal preparations.
Amrutikarana; copper; herbomineral formulation; LD50; Marana; Shodhana
Nonsteroidal antiinflammatory drugs have been widely used for the management of inflammation, pain and nociception. Gastric intolerance caused by most of the nonsteroidal antiinflammatory drugs used today restricts their use. Several approaches have been proposed to modify the parent nonsteroidal antiinflammatory drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach is one of such approaches. In the present work three nonsteroidal antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs were screened for their analgesic and antiinflammatory activity using Eddy's hot plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method, respectively. These prodrugs were also evaluated for their ulcerogenic potential. All synthesized prodrugs were found to be less ulcerogenic than their parent nonsteroidal antiinflammatory drugs and showed better activity profile in terms of analgesic and antiinflammatory activity as compared to their respective parent drugs.
NSAIDs; ibuprofen; diclofenac; flurbiprofen; ulcerogenicity
Puerarin injection has been widely used for clinic treatment of diabetes recently. To assess the relationship between the administration time of puerarin and the blood concentration of puerarin as well as its pharmacokinetic parameters, the diabetic rat model was used in current study. The rats were randomly divided into morning and evening groups according to the administration time. After the puerarin injection, blood glucose was tested in order to know whether the efficiency of puerarin was influenced by its concentration and pharmacokinetic parameters. Our results show that the average concentration of puerarin in the evening group is significantly higher than that in the morning group. The numbers of t1/2α, t1/2β, CL and AUC(0-∞) are significantly different between the morning and evening groups. The blood glucose level in the evening group was lower than that in the morning group. The speed of its onset is higher and the blood glucose level declines much more significantly in the evening group. These findings suggest that the concentration and pharmacokinetic parameters of puerarin affect its efficiency in diabetic rats. Therefore, it might be better to give puerarin in evening than in the morning for the mellitus treatment.
Chronopharmacokinetics; puerarin injection; blood glucose; variations; diabetic rats
In the current work the kinetics of dehydration of ziprasidone hydrochloride monohydrate was studied by nonisothermal thermogravimetry. Ziprasidone hydrochloride monohydrate was heated from 30 to 150° with a heating rate of 5° per min under nitrogen gas atmosphere and weight loss data were collected. Powder X-ray difraction was used to characterize the solid before and after dehydration. The well accepted Coats-Redfern model fitting approach was applied to the thermogravimetry data for the kinetic analysis. Thirteen solid state reaction models were studied; among them one-dimensional diffusion model was found to be the best fit model for this reaction with an excellent correlation 0.9994. The Arrhenius parameters, activation energy, and pre-exponential factor were determined, the values were found to be 28 k.cal/mol and 9.53×1013 sec−1, respectively.
Model fitting; kinetics; dehydration; thermogravimetry; ziprasidone hydrochloride
A simple, precise, accurate, and rapid high-performance thin layer chromatographic method has been developed and validated for the simultaneous quantitation of flunarizine dihydrochloride and propranolol hydrochloride in a combined capsule dosage form. The method was carried out on precoated silica gel 60 F254 TLC aluminum plate, (20×10 cm2). The solvent system was ethyl acetate:methanol:glacial acetic acid in the proportion of 8:1:1, (v/v/v). Rf value for flunarizine dihydrochloride and propranolol hydrochloride was found to be 0.62±0.02 and 0.18±0.02, respectively. The linearity regression analysis for calibration showed 0.999 and 0.999 for flunarizine dihydrochloride and propranolol hydrochloride with respect to peak area and height in the concentration range of 50-350 ng/spot and 500-3500 ng/spot, respectively. Accuracy of recovery studies was found to be 98-100.28 and 99.11-99.45% for flunarizine dihydrochloride and propranolol hydrochloride, respectively. The amounts of drug in marketed formulation were 100.5 and 101.25% of flunarizine dihydrochloride and propranolol hydrochloride, respectively. The method developed can be used for routine analysis in bulk drug and capsule dosage form.
Flunarizine dihydrochloride and propranolol hydrochloride; high performance thin layer chromatography; validation
The present study reports physicochemical characterization and antioxidant activity of essential oils extracted from guggul (Commiphora wightii) exudates collected from different places in Madhya Pradesh, India. The guggul exudates were hydrodistilled for 3-4 h in Clevenger apparatus. The oil obtained was dried over anhydrous Na2SO4 and stored at 4° until testing. Before extraction of oils from the exudates, their % moisture and tristimulus values of the colors namely L (white-black), a (green-red) and b (blue-yellow) were determined. Physicochemical characterization of the extracted oils was carried out to determine their solubility, yield%, acid value (mg/KOH/g), saponification value (mg/KOH/g), ester value, iodine value (g/g), peroxide value (mEq/kg) and Fourier transformed infrared analyses. The storage-effect on the % moisture and tristimulus values of the colors of guggul exudates as also the % oil yield and physicochemical parameters of the essential oils extracted from them, were studied using three different packaging materials viz., local plastic, low density polyethylene (200 G) and high density polyethylene (200 G). The antioxidant potential of extracted oils was evaluated by free radical scavenging activity using 1,1-diphenyl-2-picryl hydrazyl assay.
Guggul; Commiphora wightii; essential oil; physicochemical characterization; antioxidant activity
A stability-indicating reverse-phase high-pressure liquid chromatography method with photodiode array detector was developed and validated for estimation of riluzole in the bulk and tablet dosage forms. Riluzole was subjected to stress conditions (light, heat, humidity, acid/base hydrolysis and oxidation) and the stressed samples were analyzed by developed method. Degradation was observed in acidic, basic, oxidative and thermal conditions. The degradation products were well resolved from riluzole peak. An inertsil-ods column (250×4.6 mm, 5 μ) with a mobile phase comprising 0.02% v/v formic acid:acetonitrile(35:65 v/v) at a flow rate of 1.0 ml/min was used and eluents were monitored at 260 nm. The retention time of riluzole was 5.7 min. Complete validation for the method was carried out according to Internation Conference on Harmonization guidelines. Linearity was achieved in the range 10-50 μg/ml with a correlation coefficient (r) 0.9998. The percent assay was 100.92 and mean percentage recovery was found to be 101.10.
Riluzole; reverse phase liquid chromatography; forced degradation; validation
Preliminary phytochemical screening showed the presence of terpenes, flavonoids, tannins, alkaloids, phenolic acid, sterols, and glycosides. This study was intended to evaluate the antiinflammatory activity of various extracts of fresh leaves of Clerodendrum paniculatum Linn experimentally by in vitro (human red blood cell membrane stabilization method) and in vivo methods (0.1 ml of 1% w/v carrageenan-induced rat paw oedema model). Petroleum ether, chloroform, ethyl acetate, alcohol, and aqueous extracts were screened for in vitro antiinflammatory activity. Petroleum ether and chloroform extracts which showed, best in vitro antiinflammatory activity was screened for in vivo antiinflammatory activity at the dose level of 200 and 400 mg/kg. Indomethacin at the dose level of 10 mg/kg was used as reference standard drug. Both the extracts showed a dose dependent significant (P<0.001) reduction in paw edema when compared to the control, at all the time intervals and comparable to indomethacin (reference standard) treated group. The results of the present study demonstrate that petroleum ether and chloroform extracts possess significant (P<0.001) antiinflammatory potential which provide scientific basis for the traditional claims of Clerodendrum paniculatum Linn leaves as an antiinflammatory drug.
Antiinflammatory activity; carrageenan; Clerodendrum paniculatum Linn; human red blood cells membrane; verbenaceae
In the present study, anticonvulsant activity of methanol extract of Eclipta alba (10-200 mg/kg) was studied using pentylenetetrazole- and picrotoxin-induced seizure models. Mechanism of effect of methanol extract of Eclipta alba was further elucidated by studying its GABAA receptor modulatory activity and its effect on levels of GABA in mice brain. Methanol extract of Eclipta alba exhibited potent anticonvulsant activity but has saturation of its pharmacological activity at 50 mg/kg. At the concentration of 10 mg/ml, contractions induced in guinea pig ileum was blocked by picrotoxin, but it didn’t not show any increase in GABA levels in mice brain after treatment. Hence, it can be concluded that methanol extract of Eclipta alba possesses potent anticonvulsant activity because of its positive modulatory effect on GABAA receptors.
Epilepsy; pentylenetetrazole; picrotoxin; GABA; wedelolactone; luteolin
Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial.
Bloodletting; cancer; cardiovascular diseases; diabetes mellitus; hirudin; leech; microsurgery
The objective of this work was to increase the amount of acyclovir in the basal epidermis, site of herpes virus simplex infection, using the solid lipid nanoparticles loaded gel cream as carriers. Solid lipid nanoparticles were prepared by high pressure homogenisation method and incorporated in a semisolid submicron gel cream. Acyclovir distribution into rat skin after topical application of solid lipid nanoparticles loaded gel cream was determined by fabricated Franz diffusion cell. The results showed that, the quantity of the acyclovir in the basal epidermis with the solid lipid nanoparticles loaded submicron gel cream was two folds times more than marketed acyclovir gel cream. This type of carrier can improve acyclovir loaded therapy since it increases drug retention in the basal epidermis.
Acyclovir; homogenisation; solid lipid nanoparticles; medium chain triglyceride
The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository.
Naproxen; polyethylene glycols; suppository; surfactant; Witepsol
In the present study, we investigate the antiulcerogenic effect of gallic acid against aspirin plus pyrolus ligation-induced gastric ulcer in rats. Rats were treated with gallic acid (100 and 200 mg/kg) and famotidine (20 mg/kg) for 1 week, followed by induction of gastric ulcer using the aspirin plus pyrolus ligation model. At the end of 4 h after ligation, the rats were sacrificed and ulcer index, gastric juice volume, pH and other biochemical parameter of gastric juice were evaluated. Stomachs of rats were evaluated biochemically to determine oxidant and antioxidant parameters. Pretreatment with gallic acid significantly decreased ulcer index, gastric juice volume, free and total acidity, total protein, DNA content and increased pH and carbohydrates concentration. Gallic acid at a dose of 100 and 200 mg/kg exerted 69.7 and 78.9% ulcer inhibition, respectively. The levels of superoxide dismutase, catalase, reduced glutathione, glutathione reductase, glutathione peroxidise, glucose-6-phosphate dehydrogenase were increased while reduction in myeloperoxidase and lipid peroxidation were observed in the stomach tissues of the drug treated rats. The histopathological studies further confirmed the antiulcer activity of gallic acid. We conclude that the gallic acid possesses antiulcer effect and that these occur by a mechanism that involves attenuation of offensive factors, improvement of mucosal defensive with activation of antioxidant parameters and inhibition of some toxic oxidant parameters.
Antioxidant; antisecratoty; antiulcer; aspirin plus pylorus ligation; gallic acid; mucosal defence
To rationalize scientifically the traditional claim on use of Wedelia biflora (Linn.) D. C. for the treatment of wounds and infections, the present study was designed to evaluate the antimicrobial and wound healing activity of ethanol extract of leaves of W. biflora. In in vitro assays the test extract was subjected to antimicrobial activity by agar well-diffusion method and minimum inhibitory concentration method in different microbial strains. Wound healing activity of the test extract was studied by excision wound model and incision wound model in Wistar albino rats. In excision wound model, 97.90% wound healing was recorded in 10% w/w extract treated group on 16th days of postsurgery, whereas only 58.50% was observed in control group. In incision model, higher breaking strength, high hydroxyl proline content and histopathological study in extract treated groups revealed higher collagen redeposition than the control group. The agar well-diffusion evaluation and minimum inhibitory concentration established antimicrobial efficacy of ethanol extracts of W. biflora. These observations established the traditional claim and therapeutic activity of W. biflora and it could be a potent wound healing candidate for use in future.
Antimicrobial activity; excision wound; incision wound; Wedelia biflora