In Vitro and Vivo Pharmacology Research Papers (original) (raw)

Anticancer activity of novel compound 4-(4-(3, 4-
dimethoxyphenyl) hexahydrofuro [3,4-c]furan-1-yl)-2-
methoxyphenyl acetate isolated from Pandanus
odoratissimus was studied against Ehrlich Ascites
Carcinoma (EAC) cells in Swiss albino mice. Anticancer
activity of compound was examined by determining the
body weight, average tumor weight, tumor cell volume, cell
count, viable, mean survival time, life span and
hematological studies. Treatment of mice with this phenolic
compound resulted in a cell growth inhibition by 75.02%,
63.36%, and 27.28% at doses of 50, 25, and 10 mg/kg (i.p.)
respectively. Standard drug Vinblastine at 0.5 mg/kg (i.p.)
exhibited maximum inhibition (86.12%). The tumor bearing
mice treated with the test compound at different doses
showed significant increase in life span of mice by 29.12%,
58.78%, and 80.51% at the doses of 10, 25 and 50 mg/kg
(i.p.), respectively. The compound increased the life span of
EAC treated mice and restored the hematological
parameters. Thus, the present study reveals anticancer
potential of the tested phenolic compound against EAC in
experimental models

- by and +2
- •
- In Vitro and Vivo Pharmacology, Anticancer Drugs

Context: Pithecellobium dulce (PD) is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. Aims: To evaluate the acute and sub-acute toxicity of P. dulce stem bark hydroethanolic extract in Wistar rats. Methods: In the acute test, a single dose of 5 g/kg body weight was administered to Wistar rats afterwards they were observed individually 4 hours post-dosing, and at least once daily for 14 consecutive days. The sub-acute toxicity was evaluated by daily oral administration of 0.5 and 1 g/kg extract, for 28 days. Biochemical and hematological parameters assessment as well as body and organ weights of the rats were carried out. Results: The limit dose of 5 g/kg did not cause any mortality or signs of acute toxicity on the rats during the experimentation period. In the sub-acute test, uterus-ovary-trompe (UOT) weight decreased dose-dependently: Control group (0.82 ± 0.03 g); Extract 0.5 g/kg (0.57 ± 0.06 g); Extract 1g/kg (0.48 ± 0.01 g) (p ˂ 0.01). Extract lowered urea values in female group treated with 1 g/kg (p < 0.01). Lymphocytes percentage was dose dependently increased in treated male groups: Control group (53.00 ± 0.58%); extract 0.5 g/kg (58.67 ± 0.67%) and extract 1 g/kg (60.67 ± 2.41%). Conclusions: These findings suggest that PD is relatively safe when administered orally in rats but is slightly atrophic for female reproductive organs.

Objective structured practical examination (OSPE) a new
assessment tool has been implemented in a few medical colleges.
This method of assessment was planned to be implemented in our
medical college, before which the authors planned to compare the
scores obtained by the students by conventional method of
examination and OSPE. The marks obtained by the two methods
of examination were compared and a feedback was collected from
students to study their perspective towards OSPE. There was
statistically significant difference in the mean of the scores
obtained by conventional method and that of OSPE. The students’
perception about OSPE was good. This study enabled the authors
to standardize the pattern of OSPE and implement it.

Objective: To find out a cheap and effective remedy for Erectile dysfunction and other sexual abnormalities in male in which approximately 5–20% of men are prevalent in moderate-to-severe form (Kubin etal, 2003) Introduction: Normal sexual health in male may be broadly defined as the ability to achieve or maintain an erection sufficiently rigid for satisfying sexual intercourse. A huge amount of men especially in later age are involved in some abnormality of sexual health resulting in fear, loss of self-image and self confidence, and depression. Erectyle dysfunction can have a profound negative impact on the quality of life and life satisfaction of the patient (and his partner) and a number of males are unable to do pregnant to his female partner due to less OR unavailability of motile sperms in their semen.(Seidman,etal,2001). The medicines still available in the market for Erectyle dysfunction are sildenafil vardenafil, tadalafil, and avanafil are Phosphodiestrase(PDE5)inhibitors that are still not proven for sperm health and motility (improvement of healthy sperm count) ,(Purvis etal,2002) and also have side effects i.e disturbance in colour vision and risk for cardivescular patients (Lippincott Pharmacology 6th edition). So, space for a better medicine is always available which will be less expensive and better in quality with negligible side effects. Milk seeming from Banyan tree F. benghalensis indigenous to Indian subcontinent has long been being used by the people living in this region for different sexual abnormalities but still have not enough scientific research. So,this may have a best treatment for sexual abnormalities which need to be scientific evaluation.

- by Zahid Farooq
- •
- In Vitro and Vivo Pharmacology
- by Siti Nazila
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- Pharmacology, In Vitro and Vivo Pharmacology, Pharmacy Education
- by Gabino Garrido and +1
- •
- Pharmacology, Therapeutic Relationship, Clinical Pharmacology, Molecular Pharmacology

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect and Google Scholar with the following keyword search terms: “gout,” “medicinal plants,” “Malaysia,” “epidemiology,” “in vitro,” and “in vivo.” In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris, and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated.

Objectives: Free radical induced oxidative stress is involved in the pathogenesis of various diseases and disorders. Antioxidants play an important role against this oxidative stress to protect our body. The present study was carried out to evaluate the in vitro antioxidant properties of hydro alcoholic fruit extract of Cucurbita pepo (HFECP). Methods: HFECP was assayed on different in vitro free radical models like DPPH, FRAP, ABTS and total antioxidant assay models. Reductive ability of the extract was also tested by the complex formation with potassium ferricyanide. Further total phenolic and flavonoid contents of the crude fruit extract were also measured. Butylated hydroxy toluene was taken as standard. Result: The extract showed good dose dependent free radical scavenging activity in all the models. Reductive ability was also found to increase with increase in extract concentration. Determination of total phenolic and total flavonoids content showed that 1 gm of fruit extract contains 66.70±3.60 mg equivalent of rutin and 26.50±1.40 mg equivalent of gallic acid. Conclusion: All the results of the in vitro antioxidant assays revealed potent antioxidant and free radical scavenging activity of the fruit extract of Cucurbita pepo, equivalent to that of standard quercetin and this antioxidant property may be attributed to its high phenolic and flavonoid contents.

Withania somniferous (L.) Dunal (Family: Solanaceae, commonly known as

- by Manjusha Tyagi and +1
- •
- History of Medicine, Medicinal Chemistry, Tissue Engineering, Biotechnology

The big stores for the favorable algae are the Seas and Oceans and the study of seaweeds is called as phycology or ecology. The identification and isolation of new substances are growing from the source of marine organisms. The seaweeds live in salty water and are eukaryotic organisms considered as a good source of bioactive natural products. The present study investigated to explore the phytochemical constituents of the seaweed Sargassum wightii (Brown algae). The brown marine algae " Sargassum wightii " belongs to the family " Phaeophyceae ". Ethanol was used as a solvent system for the preparation of the extract of Sargassum wightii. The ethanolic extracts of Sargas-sum Wightii were undergone to the qualitatively phytochemical test by means of typical measures. Phytochemical analysis shows the presence of alkaloids, tannins, steroids, flavonoids, and carbohydrates, whereas proteins, free amino acids and saponins were found to be absent. The results of the study may lead a foundation for t he further studies on this marine algae Sargassum wightii.

- by Anson S Maroky
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- Pharmacology, Biochemistry, Pharmacy, Toxicology

Neurological ataxia have high social influence and are important aspect determining the prolonged healthy age and the vitality in the modern times. Some of the well known neurological ataxia are Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis and Creutzfeldt-Jakob's. According to the the United Nation's health agency, World Health Organization, mental and neurological disorders ranging from depression to Alzheimer's currently strike 400 million people universally and are set to rush in the next two decades. Non-availability of drugs for the prophylaxis and regimen of these disorders throws a confrontation for the researchers. The plentiful natural molecules of plant origin and their modification has yielded turnout not only the new lead molecules for drug discovery and development but also the nutraceuticals. Historically, Withania sominifera commonly known as Ashwagandha is being used as neurotonic for anxiety and neurological disorders. In the current study, culture conditions such as phytohormone and temperature were optimized for both direct and indirect organogenesis to obtain 61-80 shoots from nodal explants of Withania somnifera. The in-vitro cultured plantlets were rooted and reconcile for field trial conditions. The methanolic extract processed from the roots of these plantlet were subjected to HPLC for discosure of compounds.

- by Dr. Naveen Gaurav
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- History of Medicine, Tissue Engineering, Traditional Medicine, Biotechnology

Objective: Paspalum scrobiculatum (P. scrobiculatum) is a millet variety, cultivated throughout India having different pharmacological properties like antidiabetic, anti-inflammatory, hopolipidaemic, anti-rheumatic and wound healing. Various bioactive components from plant origin are studied to access their role in neurodegenerative diseases. In this study, the antidepressant effect of ethanolic extract of P. scrobiculatum (EEPS) grains was studied in mice. Method: Forced swimming test (FST) and tail suspension test (TST) were used to determine the antidepressant effect of 200 and 400 mg/kg EEPS grain extracts by oral administration to mice. Imipramine (30 mg/kg) was used as standard drug. Result: The results showed that doses, 200 mg/kg and 400 mg/kg ethanolic extracts showed antidepressant effect by significantly reducing the immobility time compared to vehicle (P<0.001), in both the models studied, similar to that of standard imipramine drug. Significant variation in immobility time of 400 mg/kg ethanolic extract was observed. Conclusion: The findings suggest that grains of P. scrobiculatum millet exert antidepressant like behavior in mice, which can be attributed to the bioactive components present in the ethanolic extract of P. scrobiculatum, which are yet to be elucidated by fractionation studies.

- by Swati Sharma
- •
- Pharmacology, Biochemistry, Pharmacy, Depression

The present study was to estimate the preliminary phytochemical screening and in vitro anti-oxidant activity of aerial part extracts of Viburnum punctatum by using solvents like Petroleum ether, Chloroform, Methanol and Water. Preliminary phytochemical analysis reveals the presence of alkaloids, glycosides, flavonoids, phenolic compounds, proteins, phytosterols and saponins. The chloroform and methanol extract were screened for its antiinflammatory activity by cyclooxygenase inhibition and lipooxygenase inhibition on Human peripheral lymphocytes cell lines using Aspirin as a standard drug. The chloroform and methanol extracts of the Viburnum punctatum was taken at three different concentrations (100μg/ml, 500μg/ml, and 1000μg/ml) and its percentage inhibition was compared with that of the standard Aspirin. The methanolic extract showed good results with that of the standard and hence proved to have Cyclooxygenase and lipo-oxygenase inhibitory activity higher than that of the chloroform extract.

Peptides obtained from three varieties of common beans (Phaseolus vulgaris L.) named plus black (PB), azufrado higuera (AH) and pinto Saltillo (PS) presented antimicrobial, antioxidant and antihypertensive activities. Peptides were obtained from these common beans protein concentrates after treatment with Alcalase® followed by ultrafiltration using 1-, 3- and 10-kDa molecular weight cutoff membranes. Antioxidant activity was determined by the 2,2′-azino-bis (3-etilbenzotiazolin-6-sulfonic) acid method and was expressed as Trolox equivalent antioxidant capacity (TEAC). The highest antioxidant activity (630, 550 and 517 mM TEAC/mg protein) was observed in the group of peptides with a molecular weight lower than 1 kDa (F < 1) from PB, AH and PS bean varieties, respectively. Antibacterial activity was determined as susceptibility test in which ten of twelve bacteria strains showed growth inhibition with the total hydrolysates (TH) and the peptidic fraction 3–10 kDa; subsequently, the minimum inhibitory concentration was determined with the standard microdilution assay in a 96-well plates in which the peptidic fraction F < 1 kDa presented antimicrobial activity against Shigella dysenteriae with the three beans varieties at 0.1, 0.4 and 0.3 mg/mL (for PB, AH and PS, respectively). Additionally to the antimicrobial and antioxidant activities, the TH of the PB and AH bean varieties presented high inhibition of the angiotensin-I-converting enzyme (ACE-I) (IC50 = 4.34 ± 0.29 and 4.82 ± 1.59 μg/mL, respectively). And, when the peptidic fraction F3–10 kDa was tested, the AH variety showed a significant increase in the ACE-I capacity (IC50 = 1.09 ± 0.04 μg/mL). Importantly, this peptidic fraction decreased the systolic blood pressure in a spontaneously hypertensive rat model after 2 h of administration by a single interperitoneally dose.

- by Teresita Ariza
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- Antimicrobials, Antioxidants, Hypertension, In Vitro and Vivo Pharmacology

implications for global health. It is the fourth leading cause of
death in the United States, exceeded only by heart attacks, cancers,
and stroke. This can result from several types of anatomical
lesions, including loss of lung elastic recoil and fibrosis and
narrowing of small airways. Inflammation, edema, and secretions
also contribute variably to airflow limitation. Occupational
exposure to dusts and chemicals, asthma, age, tobacco smoke and
genetic factors likely play a major role and which also account for
much of the heterogeneity susceptibility to smoke and other
factors. Many factors may play a role, but to date, only α-1
protease inhibitor deficiency has been unambiguously identified.
Exposures other than cigarette smoke can also contribute to the
development of COPD. Spirometry is recommended in COPD
guidelines for the accurate diagnosis of this disease. Wheezing,
productive cough, barrel chest and shortness of breath are some of
the hallmark signs of COPD. Although COPD cannot be cured
but it can be managed my reducing symptoms and improving
overall health, WHO and NICE have guidelines regarding COPD
which outline management via pharmacotherapy for approaching
COPD. The advances in understanding the pathogenesis of COPD
have identified the provided therapy for management of this
disease, if these guidelines are accurately followed, reduction in
further complications or mortality from this ailment can be
achieved.

Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for new, more affordable and accessible antimalarial agents possessing original modes of action. Natural products have played a dominant role in the discovery of leads for the development of drugs to treat human diseases, and this fact anticipates that new antimalarial leads may certainly emerge from tropical plant sources. This present review covers most of the recently-published nonalkaloidal natural compounds from plants with antiplasmodial and antimalarial properties, belonging to the classes of terpenes, limonoids, flavonoids, chromones, xanthones, anthraquinones, miscellaneous and related compounds, besides the majority of papers describing antiplasmodial crude extracts published in the last five years not reviewed before. In addition, some perspectives and remarks on the development of new drugs and phytomedicines for malaria are succinctly discussed.

- by Ronan Batista
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- Natural Products, Natural Products Chemistry, Metabolism, Malaria

Diabetes mellitus is a chronic metabolic disorder affecting about 6% of population worldwide with its complications and is rapidly reaching epidemic scale. Cinnamomum zeylanicum is widely used in alternative system of medicine for treatment of diabetes. In the present study, we have performed bioassay guided fractionation of chloroform extract of C. zeylaniucm and identified cinnamaldehyde (CND) as an active principle against diabetes. In continuation to it, a detailed study was undertaken to elucidate its mode of antidiabetic action in STZ induced diabetic rats. Oral administration of CND (20 mg/kg bw) to diabetic rats for 2 months showed significant improvement (p < 0.001) in muscle and hepatic glycogen content. In vitro incubation of pancreatic islets with CND enhanced the insulin release compared to glibenclamide. The insulinotropic effect of CND was found to increase the glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues. The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels.

- by Prachi Anand
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- Biochemistry, Natural Products, Natural Products Chemistry, Diabetes

Eucalyptus plant belongs to the Myrtaceae (Myrtle) family. Eucalyptus is a tall evergreen tree native to Australia, nowadays found around the world. Eucalyptus Plants have been used for the treatment of diseases for a very long time. The leaves and oil of the eucalyptus plant are used for medicinal purposes. The plant and its extracts have been evaluated for a number of activities, namely, antimicrobial, antispasmodic, antifungal, antiseptic, bronchitis, deodorant, diabetes, skin diseases, anti-inflammatory, analgesic, anti-arthritic and antipyretic. During the present study, the plant was subjected to genotoxicity studies viz. bacterial reverse mutation test (Ames Test) in order to ascertain an aspect of the safety of the drug and ecosystem. Eucalyptus globulusleaf extracts showed no mutagenicity when tested with difference revertants of Salmonella typhimuriumviz. TA98, TA100, TA102, TA1535 and TA1537in presence and absence of metabolic activation system (S9). In addition, the extract showed significant protective effect against mutagenicity induced by mutagen in S. typhimurium TA98 and TA100 strains with or

- by JASWANT RAY
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- Genetics, Microbiology, Bacteriology, Toxicology

This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of 1 H, 13 C NMR and crystallographic data for two novel entkaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of entkaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.

- by Ronan Batista and +1
- •
- Organic Chemistry, Cancer, Malaria, Biological Activity Of Natural Products

Aim: To determine the prescribing rate and pattern of antiparkinson drug use and to assess associated adverse drug reactions in patients with idiopathic Parkinson disease.
Materials and methods: Data was collected from the outpatients in neurology and medical records department. Patient demography, disease duration, symptoms, comorbid conditions, drug, dose, adverse drug reaction if any were noted. Information was collected again from the study participants during their routine follow up visit three months later to monitor the symptoms and adverse drug reactions (if any) occurring due to treatment. Causality assessment was done for the ADRs reported based on WHO scale.
Results: Male predominance was seen. A majority of patients were between 51 and 80 years and most of the patients had onset of disease between 51 and 70 years. The common presenting symptoms were rigidity, tremor and bradykinesia. Out of 100 patients, 48 received levodopa+carbidopa alone and the rest received combination therapy. The number of antiparkinson drug prescriptions increased with the disease duration. Sixty three patients had subjective improvement in the symptoms, of which bradykinesia was most common. Levodopa induced dyskinesia was the most common adverse drug reaction. The number of adverse drug reactions was significantly higher among patients receiving combination therapy.
Conclusion: Our study provides a basic knowledge about the drug prescribing pattern in the treatment of Parkinson disease and also the adverse reactions to the drugs prescribed.

A nanostructured lipid carrier (NLC) loaded with doxorubicin (DOX) has been shown to be cytotoxic against the human cancer cell lines A549 and MCF-7/Adr. In attempts to improve formulation characteristics, enhance pharmacokinetics and antitumor effects, we modified the surface of these NLC with an alternating layer-by-layer (LbL) assembly of polycation and polyanion polyelectrolytes and an additional coating with PEG using a simple method of core shell attachment. The formulation had a narrow size distribution, longer residence in the blood, lower accumulation in the liver, higher
accumulation in tumors and a significant tumor growth inhibition effect. Thus, NLC–DOX nanopreparations complexes modified by LbL coating have the potential to enhance the anticancer effects of
DOX against tumors.

Oocyte, embryo and ovarian tissue cryopreservation are being increasingly proposed for fertility preservation among cancer patients undergoing therapy to enable them to have babies after the cancer is cured. Embryo cryopreservation is not appropriate for single girls without any spermpartner. It is impossible in cases requiring immediate cancer cure because oocyte retrieval is an extended procedure. Thus ovarian tissue cryopreservation has been suggested for fertility preservation especially in cancer patients. The main goal of ovarian cryopreservation is re-implanting the tissue into the body to restore fertility and the hormonal cycle. Different cryopreservation protocols have been examined and established for vitrification of biological samples. We have used Cryopin to plunge ovarian tissue into the liquid nitrogen and promising results have been observed. The possibility of recurrence of malignancy in the reimplanted tissue could be a problem. Xenografting-implantation of the preserved tissue in another species-also has its drawbacks such as molecular signaling from the recipient. In vitro follicle culturing is a safer method to obtain mature oocytes for fertilization and the various studies that have been carried out in this area are reviewed in this paper.

- by Cell Journal Yakhteh
- •
- Cancer, In Vitro and Vivo Pharmacology

The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents.

The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/ day) for 72 hours has exhibited slightly better anxiolytic effect (p < 0.05) through the time span (92.33 & 93.33 s) spent in the opened arms of EPM vs. diazepam (1 mg/kg b.w i.p/day; 69.33 s). In HBT, only WSE (200 mg/kg b.w/day) has shown a promising number of mean head pokes (13.27 times/min) vs. diazepam (12.87 times/min). The WSE (62.5-500 mg/mL) exposure has exhibited 40.14-72.18% protection against lysis of RBCs vs. aspirin (57.04-71.48%) whilst 62.67-67.66% inhibition of protein denaturation vs. diclofenac sodium (43.11-80.64%). The current findings suggested WSE has promising anxiolytic and anti-inflammatory activities.

Intracortical neural probes enable researchers to measure electrical and chemical signals in the brain. However, penetration injury from probe insertion into living brain tissue leads to an inflammatory tissue response. In turn, microglia are activated, which leads to encapsulation of the probe and release of pro-inflammatory cytokines. This inflammatory tissue response alters the electrical and chemical microen-vironment surrounding the implanted probe, which may in turn interfere with signal acquisition. Dexamethasone (Dex), a potent anti-inflammatory steroid, can be used to prevent and diminish tissue disruptions caused by probe implantation. Herein, we report retrodialysis administration of dexa-methasone while using in vivo two-photon microscopy to observe real-time microglial reaction to the implanted probe. Microdialysis probes under artificial cerebrospinal fluid (aCSF) perfusion with or without Dex were implanted into the cortex of transgenic mice that express GFP in microglia under the CX3CR1 promoter and imaged for 6 h. Acute morphological changes in microglia were evident around the microdialysis probe. The radius of microglia activation was 177.1 mm with aCSF control compared to 93.0 mm with Dex perfusion. T-stage morphology and microglia directionality indices were also used to quantify the microglial response to implanted probes as a function of distance. Dexamethasone had a profound effect on the microglia morphology and reduced the acute activation of these cells.

The evolution and subsequent design of clinically effective antima-larial drugs particularly 4-aminoquinolines, 8-aminoquinolines and 9-amino-acridines are reviewed. These molecules benefited from scientific advances in medicinal and synthetic chemistry guided by pharmacological screening, including animal models of malaria. The mechanism of action of antimalarials, especially against the heme receptor, and the impact of this knowledge on drug design is critically discussed. Modelling investigations and quantum mechanics calculations reveal close contacts between the porphyrin ring and selected atoms within compounds such as the bisquinoline, metaquine. Analysis of these close contacts can be used to design compounds with modulated antimalari-al activity to further clarify the drug action. Knowledge of mammalian drug metabolism and pharmacokinetics, together with detailed in vitro and in vivo pharmacology has aided (a) resurrection of old compounds and (b) redesign of existing compounds. The latter includes judicious modification (e.g. inversion of oxidizable functional groups as in SN-13,730 i.e. isoquine) or introduction of groups blocking metabolism (e.g. exploiting bond strength viz. fluorine or steric effects with the t-butyl group). This simultaneous modulation of both drug metabolism and interaction with the heme receptor can be used to enhance antimalarial activity. Compounds benefiting from such modifications include primaquine, pyronaridine, isoquine, metaquine and AQ-13, together with selected analogues with useful activity against drug-resistant Plasmodia in vi-vo. It is concluded that optimisation of the privileged quinoline and acridine scaffolds, discovered in the early part of the 20 th century, still has a vital role to play in the future discovery of cost effective solutions to malaria.

- by fyaz Ismail
- •
- Computer Science, History of Science, Drug Designing, Computer Aided Design

The purpose of the present study was to explore the possible morphological features and growth patterns of calcium oxalate monohydrate crystals. The study was carried out on a glass slide under microscope. The results showed that the calcium oxalate monohydrate crystals may be present in the form of arborescent, donut, dumbbell, needles, platy, prismatic, rosette, round edges, loose agglomerates and compact aggregates. The study provides detailed information about the morphology and aggregation patterns of calcium oxalate monohydrate crystals.

- by Salman Ahmed
- •
- Pharmacy, Chronic kidney disease, Pharmacognosy, Phytomedicine

Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD) analysis, differential thermal analysis (DTA), and scanning electron microscopy (SEM). To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen). The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan's Multiple Range Test (95% confidence interval). The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.

Concurrent administration of more than one drug is a common practice in medical science and in such case one drug may affect the pharmacology of another drug. Ciprofloxacin is a commonly used antibiotic in Bangladesh and frequently prescribed with paracetamol and zinc salt for concomitant use in patients suffering from infections. Therefore, the interaction of ciprofloxacin with paracetamol and zinc salt was studied in vitro at pH 1.2, 6.8 and 7.4 which are related to gastric, intestinal juices and blood environment, respectively. In vitro evaluation of ciprofloxacin complexes with paracetamol and zinc was carried on several gram positive and gram negative microorganisms by disc diffusion method. The in vivo effect of the complexes was assessed by determining the plasma concentration in mice by spectroscopic method. It was observed that in the in vitro study paracetamol and zinc has insignificant effect on the antibacterial activity of ciprofloxacin although zinc itself showed so...

- by Dr. Md. Zakir Sultan
- •
- Chemistry, Interaction, In Vitro and Vivo Pharmacology, Key words

Clerodendrumnviscosum vent.isa majestic and broadly used medicinal plant in Bangladesh and India. This research work was carried out to evaluate the phytochemical and biological activity of Clerodendrumviscosum vent. The powdered barks of the roots were extracted with ethanol by a soxhlet apparatus. Ethanol extract was subjected to TLC (Thin Layer Chromatography) examination. A single spot was observed in n-hexane ethyl acetate (4:1) with Rf values 0.5. Phytochemical screening of the ethanol extract showed the presence of carbohydrates, steroids, tannins, flavonoids, saponines and alkaloids. The crude ethanol extract showed toxic behavior against brine shrimp lethality bioassay. The mortality rate of brine shrimp was found to be increased with the increase in concentration of the sample. From the result on the brine shrimp lethality bioassay it can be well predicted that the crude extracts have considerable cytotoxic potency.

- by zubair labu
- •
- Biochemistry, Phytochemistry, Cell Culture, real time PCR

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox...

- by J. Zasadzinski
- •
- Targeted Drug Delivery, Nanobiotechnology, Nanoparticles, Confocal Microscopy

Introduction
Hydrogen sulfide (H2S) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation.
Objectives
We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties.
Methods
All the molecules are characterized for their ability to release H2S both via amperometric approach and using a fluorescent probe. The chemical stability of the newly synthesized hybrid molecules has been investigated at differing pH values and in human serum.
Results
Prednisone-TBZ hybrid (compound 7) was selected for further evaluations. The obtained results from the in vitro and in vivo studies clearly show evidence in favor of the anti-inflammatory properties of the released H2S.
Conclusions
The protective effect on airway remodeling makes the hybrid Prednisone-TBZ (compound 7) as a promising therapeutic option in reducing allergic asthma symptoms and exacerbations.

- by Simone Brogi
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- Asthma, In Vitro and Vivo Pharmacology, Hydrogen Sulfide, Corticosteroids

"Emergence of new strains of Escherichia coli with the ability of resistance to a wide range of antibiotics necessitates the efforts to search alternatives for better treatments to deal with these infections. Chamomile is one of the most widely used herbs in the world. In this study we investigated the potential therapeutic effects of chamomile chloroform extract on E. coli intraperitoneal (IP) infection of BALB/c mice. Female BALB/c with an average weight of 20 to 25 g, were divided into 8 groups. Lethal dose of the E. coli for mice was injected IP in test groups and treated with 5.25, 10.5 and 21 mg/mL of chamomile chloroform extract. The combined effect of the extract (50 µg/mg) with amikacin and amikacin alone were also examined. The highest number of survived mice at the dose of 10.5 mg/mL of extract and the highest death rate with 5.25 mg/mL of extract was observed. In amikacin group all infected animals were survived. Mortality rate in chamomile extract combination with amikacin is almost the same as amikacin alone. The significant lowest mortality rate was observed in the some group which had been treated with a combination of extract and amikacin. The result of this study does not recommend in-vivo using of chloroform extracts of chamomile for E.coli infection via IP administration. In vivo chloroform extracts of chamomile, it seems not to have a strong antibacterial effect on E. coli IP infection of BALB/c mice."

The aim of present study was to estimate the in vitro antioxidant activity of aqueous extract of Cucumis callosus (Rottl.) Cogn (Cucurbitaceae) seeds which is commonly known as "Kachri" in Rajasthan (India) evaluated by using DPPH radical scavenging activity and hydrogen peroxide radical scavenging activity. The antioxidant activity is compared with ascorbic acid as standard. The IC 50 values of Cucumis callosus and ascorbic acid were found 37.71 µg/ml and 16.72 µg/ml respectively for the DPPH radical scavenging activity while 94.71 µg/ml and 143.45 µg/ml respectively for hydrogen peroxide radical scavenging activity. Thus, aqueous extract of Cucumis callosus seeds possess potent antioxidant activity in hydrogen peroxide model and may be useful for preparation of neutraceuticals as potent antioxidant to treat various human diseases.

- by Dr. Bhupendra K Kumawat
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- In Vitro and Vivo Pharmacology
- by Zoltan Dekan
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- Pharmacology, Peptide Chemistry, Peptide Synthesis, Pain Management

Hashemi et al.: Inhibition of Colon Cancer Cells Proliferation and Invasion Formulating etoposide into a nanoemulsion based on combining two natural oils, Ribes nigrum (black currant) seed oil and organic evening primrose oils may improve its antineoplastic activity in cancer cells. The present study aimed to synthesize, characterize and in vitro evaluate the cytotoxic effect of formulating etoposide-loaded (black currant) seed oil and organic evening primrose oils on Colorectal Carcinoma colon cancer cells. The anti-proliferation and anti-invasion effects of the produced formula on Colorectal Carcinoma were investigated by the cell counting kit-8 and the collagen-based cell invasion assay, respectively. Mitochondrial staining kit, annexin Fluorescein isothiocyanate double staining, and nucleosome detection were used to discriminate the stages of apoptosis. According to the dynamic light scattering results, formulating etoposide-loaded (black currant) seed oil consisted of nanodroplets with z-average diameters of 144.6±5.3 nm and mean surface charge of-0.081±0.001 mV. Only (1.7±1.3) µM of formulating etoposide-loaded (black currant) seed oil was able to cause 50 % reduction in the Colorectal Carcinoma cellular growth which was strikingly lower than that of free-formulating etoposide (18.1±2.5 µM) by around tenfold. The superior apoptotic effect of Formulating etoposide Ribes nigrum (black currant) seed oil and organic evening primrose oils relative to free-formulating etoposide on the Colorectal Carcinoma cells was ascertained by the enhanced mitochondrial depolarization, higher nucleosomal ratio and increased amount of early and late apoptotic cellular populations. The Formulating etoposide Ribes nigrum (black currant) seed oil and organic evening primrose oils treatment impeded the invasion of colorectal carcinoma cells by (54.8±1.2) %, which was greater than the free-formulating etoposide treatment that deterred only (35.1±1.2) % of the invaded cells. In conclusion, the incorporation of formulating etoposide into a nanoemulsion formulated from the bioactive natural oils potentiates its antitumor activity in colon cancer cells.

- by Mayson H . Alkhatib
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- Pharmacy, Surface Science, Cytotoxicity, Colorectal cancer

Compelling human genetic studies have identified the voltage-gated sodium channel NaV1.7 as a promising therapeutic target for the treatment of pain. The analgesic spider venom-derived peptide µ-theraphotoxin-Pn3a is an exceptionally potent and selective inhibitor of NaV1.7, however, little is known about the structure-activity relationship or channel interactions that define this activity. We rationally designed seventeen Pn3a analogues and determined their activity at hNaV1.7 using patch-clamp electrophysiology. The positively charged amino acids K22 and K24 were identified as crucial for Pn3a activity, with molecular modeling identifying interactions of these residues with the S3-S4 loop of domain II of hNaV1.7. Removal of hydrophobic residues Y4, Y27 and W30 led to a loss of potency (>250-fold), while replacement of negatively charged D1 and D8 residues with a positively charged lysine led to increased potencies (>13-fold), likely through alterations in membrane lipid interactions. Mutating D8 to an asparagine led to the greatest improvement in Pn3a potency at NaV1.7 (20-fold), whilst maintaining >100-fold selectivity over the major off-targets NaV1.4, NaV1.5 and NaV1.6. The Pn3a[D8N] mutant retained analgesic activity in vivo, significantly attenuating mechanical allodynia in a clinically relevant mouse model of post-surgical pain at doses 3-fold lower than wild-type Pn3a, without causing motor adverse effects. Results from this study will facilitate future rational design of potent and selective peptidic NaV1.7 inhibitors for the development of more efficacious and safer analgesics but also to further investigate the involvement of NaV1.7 in pain.

- by Alexander Mueller
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- Pharmacology, Peptide Chemistry, Peptide Synthesis, Pain Management

• Asbestos bodies around chrysotile, crocidolite and erionite fibres inoculated in white rats were studied. • Asbestos bodies are observed after about 40 weeks from chrysotile and crocidolite but do not form from erionite. • The size of the fibres controls the formation of asbestos bodies. • The source of iron to form the asbestos bodies is organic because the dissolution of the fibres is very limited. • A model explaining the formation of asbestos bodies in chrysotile and crocidolite is postulated. a b s t r a c t This work presents a comparative FEG–SEM study of the morphological and chemical characteristics of both asbestos bodies and fibres found in the tissues of Sprague–Dawley rats subjected to intraperitoneal or intrapleural injection of UICC chrysotile, UICC crocidolite and erionite from Jersey, Nevada (USA), with monitoring up to 3 years after exposure. Due to unequal dosing based on number of fibres per mass for chrysotile with respect to crocidolite and erionite, excessive fibre burden and fibre aggregation during injection that especially for chrysotile would likely not represent what humans would be exposed to, caution must be taken in extrapolating our results based on instillation in experimental animals to human inhalation. Notwithstanding, the results of this study may help to better understand the mechanism of formation of asbestos bodies. For chrysotile and crocidolite, asbestos bodies are systematically formed on long asbestos fibres. The number of coated fibres is only 3.3% in chrysotile inoculated tissues. In UICC crocidolite, Mg, Si, and Fe are associated with the fibres whereas Fe, P and Ca are associated with the coating. Even for crocidolite, most of the observed fibres are uncoated as coated fibres are about 5.7%. Asbestos bodies do not form on erionite fibres. The crystal habit, crystallinity and chemistry of all fibre species do not change with contact time, with the exception of chrysotile which shows signs of leaching of Mg. A model for the formation of asbestos bodies from mineral fibres is postulated. Because the three fibre species show limited signs of dissolution in the tissue, they cannot act as source of elements (primarily Fe, P and Ca) promoting nucleation and growth of asbestos bodies. Hence, the limited number of coated fibres should be due to the lack of nutrients or organic nature.

The aim of present study was to estimate the in vitro antioxidant activity of alcoholic extract of Cucumis callosus (Rottl.) Cogn (Cucurbitaceae) seeds which is commonly known as "Kachri" in Rajasthan (India) evaluated by using DPPH radical scavenging activity and hydrogen peroxide radical scavenging activity assay. The antioxidant activity was compared with ascorbic acid as standard. The IC 50 values of Cucumis callosus and ascorbic acid were found 41.99 μg/ml and 24.27 μg/ml respectively for the DPPH radical scavenging activity while 95.27 μg/ml and 153.35 μg/ml respectively for hydrogen peroxide radical scavenging activity. Thus, alcoholic extract of Cucumis callosus seeds possess potent antioxidant activity in hydrogen peroxide model and may be useful for preparation of neutraceuticals as potent antioxidant to treat various human diseases.

- by Dr Tara Chand
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- In Vitro and Vivo Pharmacology

An expanding corpus of research details the relationship between functional magnetic resonance imaging (fMRI) measures and neuronal network oscillations. Typically, integrated electroencephalography and fMRI, or parallel magnetoencephalography (MEG) and fMRI are used to draw inference about the consanguinity of BOLD and electrical measurements. However, there is a relative dearth of information about the relationship between E/MEG and the focal networks from which these signals emanate. Consequently, the genesis and composition of E/MEG oscillations requires further clarification. Here we aim to contribute to understanding through a series of parallel measurements of primary motor cortex (M1) oscillations, using human MEG and in vitro rodent local field potentials. We compare spontaneous activity in the ∼10 Hz mu and 15-30 Hz beta frequency ranges and compare MEG signals with independent and integrated layers III and V (LIII/LV) from in vitro recordings. We explore the mechanisms of oscillatory generation, using specific pharmacological modulation with the GABA-A alpha-1 subunit modulator zolpidem. Finally, to determine the contribution of cortico-cortical connectivity, we recorded in vitro M1, during an incision to sever lateral connections between M1 and S1 cortices. We demonstrate that frequency distribution of MEG signals appear have closer statistically similarity with signals from integrated rather than independent LIII/LV laminae. GABAergic modulation in both modalities elicited comparable changes in the power of the beta band. Finally, cortico-cortical connectivity in sensorimotor cortex (SMC) appears to directly influence the power of the mu rhythm in LIII. These findings suggest that the MEG signal is an amalgam of outputs from LIII and LV, that multiple frequencies can arise from the same cortical area and that in vitro and MEG M1 oscillations are driven by comparable mechanisms. Finally, cortico-cortical connectivity is reflected in the power of the SMC mu rhythm.

Resumen Context: Pithecellobium dulce (PD) is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. Aims: To evaluate the acute and sub-acute toxicity of P. dulce stem bark hydroethanolic extract in Wistar rats. Methods: In the acute test, a single dose of 5 g/kg body weight was administered to Wistar rats afterwards they were observed individually 4 hours post-dosing, and at least once daily for 14 consecutive days. The sub-acute toxicity was evaluated by daily oral administration of 0.5 and 1 g/kg extract, for 28 days. Biochemical and hematological parameters assessment as well as body and organ weights of the rats were carried out. Results: The limit dose of 5 g/kg did not cause any mortality or signs of acute toxicity on the rats during the experimentation period. In the subacute test, uterus-ovary-trompe (UOT) weight decreased dosedependently: Control group (0.82 ± 0.03 g); Extract 0.5 g/kg (0....

- by Hana Starobova
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- Pharmacology, Peptide Chemistry, Peptide Synthesis, Pain Management

ABSTRACT Bone tissue engineering is an efficient approach to regenerating bone-related defects. The optimal scaffold used for bone tissue engineering must possess adequate porosity and suitable mechanical properties. This work described the development of a biodegradable polymeric composite based on polycaprolactone (PCL) and starch that can form a porous structure in situ. The scaffold exhibited the required mechanical properties at the initial stage of implantation by controlling in situ degradation and subsequent pore formation. PCL/starch (SPCL) scaffolds with 100/0, 70/30, and 50/50 ratios were developed. Degradation studies were performed in phosphate buffer saline (PBS) containing α-amylase or lipase at 37 °C for 4 weeks. Fourier-transform infrared spectroscopy was used to analyze chemical bonds and their changes after degradation. Differential scanning calorimetry was applied to determine the crystallinity and recrystallization of samples before and after degradation. Mass loss and starch release were observed during degradation, and the porosity of samples was measured by the ethanol replacement method. Morphology was further determined using scanning electron microscopy. Finally, variations in compressive strength and modulus during degradation and pore formation were also measured. The intensity of samples reached 45% after 1 month of degradation, and mechanical properties were still appropriate for human bone tissue. Reduction in mechanical property after mass loss, starch release and pore formation was controlled by the hydrogen bonding and recrystallization effect of PCL after degradation. Results suggested that SPCL composite had potential to form porous scaffold with adequate mechanical properties in situ and is promising for bone tissue engineering applications.

- by Mehran Solati-Hashjin
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- Materials Engineering, Mechanical Engineering, Bone and Antler, Starch

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening. According to the FDA's Adverse Event Recording System, 2.3 million reports of adverse drug effects were submitted across 6000 registered compounds between 1969 and 2002 1. During this period, 75 drugs or drug products were removed from the market due to these unpredicted effects, and a further 11 were given special requirements or restrictions 1. In addition to withdrawn compounds, only 1 in 10 drugs entering clinical trials typically proves efficacious enough to become registered for human treatments 2 , indicating a significant proportion of compounds validated during preclinical screening have unpredicted problems when introduced into living human systems. The high failure rate of drugs at this late stage of development contributes significantly to this increase in cost as well as delays in the development of new and more effective clinical treatments. The generation and characterization of in vitro systems capable of reproducing the functionality of specific human organs in a quantifiable manner is currently a focal point of intensive research and development given the long-standing inadequacies inherent to the use of conventional preclinical techniques for predicting human tissue behavior 3-5. Such advanced in vitro systems are seen by many as the means to streamline current drug development protocols, and thought to generate more informative platforms with which to investigate human tissue physiology and pathology in defined and controllable environments 5. Current high-throughput systems for drug discovery and toxicology applications rely on indirect measurement of cell health and function, such as biomarkers and RNA expression analysis. The field would benefit from more advanced systems that are low cost and utilize defined media to support multiple cell types under continuous flow conditions with reproducible functional readouts. Attempts to observe and characterize the interaction between multiple cell types in vitro have already been achieved to some degree. For example, co-culture of gut epithelial Caco-2 cells with hepatocytes has been performed using trans-well membranes 6 , and multiple cell types have been successfully maintained by simply establishing all cultures in confined spaces within a single culture well 7,8. However, these examples lack the dynamic flow of nutrients and toxins generated in living systems for extended time periods (> 7 days). Microfluidic

Abstract
Background: The study of the cerebrovascular physiology is crucial to understand the pathogenesis of neurological
disease and the pharmacokinetic of drugs. Appropriate models in vitro often fail to represent in vivo physiology. To
address these issues we propose the use of a novel artificial vascular system that closely mimics capillary and
venous segments of human cerebrovasculature while also allowing for an extensive control of the experimental
variables and their manipulation.
Results: Using hollow fiber technology, we modified an existing dynamic artificial model of the blood–brain barrier
(BBB) (DIV-capillary) to encompass the distal post-capillary (DIV-venules) segments of the brain circulatory system.
This artificial brain vascular system is comprised of a BBB module serially connected to a venule segment. A pump
generates a pulsatile flow with arterial pressure feeding the system. The perfusate of the capillary module achieves
levels of shear stress, pressure, and flow rate comparable to what observed in situ. Endothelial cell exposure to flow
and abluminal astrocytic stimuli allowed for the formation of a highly selective capillary BBB with a trans-endothelial
electrical resistance (TEER; >700 ohm cm2) and sucrose permeability (< 1X10-u cm/sec) comparable to in vivo. The
venule module, which attempted to reproduce features of the hemodynamic microenvironment of venules, was
perfused by media resulting in shear stress and intraluminal pressure levels lower than those found in capillaries.
Because of altered cellular and hemodynamic factors, venule segments present a less stringent vascular bed (TEER
<250 Ohm cm2; Psucrose > 1X10-4 cm/sec) than that of the BBB. Abluminal human brain vascular smooth muscle
cells were used to reproduce the venular abluminal cell composition.
Conclusion: The unique characteristics afforded by the DIV-BBB in combination with a venule segment will
realistically expand our ability to dissect and study the physiological and functional behavior of distinct segments of
the human cerebrovascular network.

- by Damir Janigro
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- Modeling, Epilepsy, In Vitro and Vivo Pharmacology, Blood brain barrier

Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired wound care modalities. Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds.

- by Claudia Moia
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- Wound Healing, Nanomaterials, Nanotechnology, In Vitro and Vivo Pharmacology