Search results for “PPAR

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33 articles

Rehabilitation With Corticobasal and Compressive Implants with Polished Surface in Case of Failure with Two Stage Implants-Article

Feb 2026 DOI 10.14302/issn.2473-1005.jdoi-25-5935
Romulus Calin FodorCorresponding author

The aim of this article is to present alternative possibilities for corrective intervention using corticobasal implants, following the failure of treatment with two stage implant in cases of extensive edentulism, multi-segmented edentulism, and the development of peri-implantitis 1 at the level of these implants. For this purpose, a case was selected involving a patient treated with two stage implants in a multi-segmented manner, in the distal regions of the maxilla and mandible, where the implants were affected after 12 years by peri-implantitis in proportions ranging from 20% to 100% in different areas of bone, with a predominance in the vestibular area. The decision was made to remove the affected two stage implants, as well as the remaining deciduous teeth, with or without periodontal conditions, but whose position on the arch made improperly rehabilitation, both functionally and aesthetically impossible, and made the second rehabilitation with polished corticobasal and compressive implants in immediate loading 2. Function and aesthetics of the gnathological apparatus were restored through definitive fixed metal-ceramic prosthetics on the support of corticobasal and compressive implants within 4 days from the beginning of the treatment, with the result being monitored over a period of 3 years and 3 months, and this evaluation is to continue over time. From a surgical perspective, for secondary rehabilitation with polished corticobasal and compressive implants, strategic positions in the maxillary and mandibular bones were used as follows: the fusion area of the maxillary bone with the sphenoid bone, the nasal cortex, the sinus cortex the lingual cortex distal to the mylohyoid line, and the interforaminal mandible area.34 These areas correspond to methods described in Consensus Number 6 in the IF The Foundation of Knowledge 5. In conclusion, the treatment with corticobasal, compressive polished implants is successful even in the case of a difficult clinical scenario like the one described for this patient 6. The reduced treatment time, along with the absence of the need for sinus lifts or bone grafts, makes it the ideal solution in any situation. The use of corticobasal implants, with fixation in the second/third cortical layer and an immediate loading protocol, should represent the primary solution in treating cases with poor bone representation, and no only as a “Corrective Intervention with Corticobasal® Implants”7.

Veterinary Healthcare Open Access

The Effects of L Carnitine on in Vitro Maturation of Immature Bovine Oocytes

Dec 2025 DOI 10.14302/issn.2575-1212.jvhc-24-4889
A Elmetwally MohammedCorresponding author

L-Carnitine (Lc) acts as an antioxidant that neutralizes free radicals, especially superoxide anions and protects cells against oxidative damage-induced apoptosis, as following ovulation, intracellular reactive oxygen species (ROS) accumulation increases in oocytes, Oocytes exhibit an intracellular defense mechanism against an oxidative attack. This outcome adversely affects fertilization and subsequent embryonic development, thereby increasing the risk of an early miscarriage and abnormal development of offspring. The purpose of this study was to see how adding LC to either maturation or fertilization medium affected the developmental competence of immature bovine oocytes. In this study, Ovaries from apparently normal reproductive organs of cattle were collected within 30 minutes from slaughter and evisceration of animals. Cumulus oocyte complexes (COCs) were collected by aspiration of medium sized ovarian follicles (4-8 mm). COCs of acceptable quality were selected, washed and incubated in tissue culture media 199 (TCM199) supplemented with 10% heat inactivated fetal calf serum, 5 μg/ml luteinizing hormone (LH), 0.5 μg/ml follicle stimulating hormone (FSH) and 1 μg/ml estradiol-17β for 20:22 hour at 38.5 C◦ under 5% CO2 in air with 90% humidity. different concentrations of LC (1.25,2.5 and 5mM) were used. The results were consistent for both maturation and fertilization and there is a significant increase in maturation, fertilization., cleavage and blastocyst rate. In conclusion, LC has important role in IVEP through addition of LC to maturation media or culture media it improved nuclear maturation and blastocyst formation rates in bovine oocytes.

Veterinary Healthcare Open Access

The Dietary Cation Anion Balance Exacerbates the Effects of Inorganic Phosphates on Parameters of Phosphate Metabolism in Cats

Jul 2024 DOI 10.14302/issn.2575-1212.jvhc-24-5146
C SteffenCorresponding author

Dietary intake of inorganic phosphates is linked to various adverse health effects. Excessive intake of highly soluble inorganic phosphates, which are used as feed and food additives, have been found to impair parameters of kidney health. As chronic kidney disease represents one of the most frequently occurring terminal diseases especially in cats, extensive knowledge regarding the safety of these additives is important. Other minerals, such as calcium, can modulate their effects on the phosphate homeostasis and kidney health. Therefore, it is crucial to examine further factors, such as the dietary cation-anion balance (CAB), resulting from the concentrations of major minerals in a diet. In this study, eleven healthy cats were fed a control diet and two diets with added sodium monophosphate (NaH2PO4) with either a low (-10 mmol/kg dry matter) or high (+450 mmol/kg dry matter) CAB for 28 days each. The serum concentrations of phosphate and parameters of phosphate homeostasis were determined in the fasting and postprandial blood samples next to the apparent digestibility and retention of phosphate and calcium. The diet with positive CAB led to an increase of serum phosphate and the phosphatonin FGF23, apparently digested phosphate, and phosphate retention. This is further proof that source and amount of phosphates in a diet are not the only determinants of the extent of potential adverse health effects. Until the interactions between inorganic phosphates and other dietary compounds are fully understood, recommendations regarding the safe use of phosphate containing additives in pet food are precarious.

Water Open Access

Scrutinizing Famine Disaster Based On Rainfall Trend Investigation (A Case Study of Khorasan Razavi Province)

May 2022 DOI 10.14302/issn.2769-2264.jw-22-4086
Gheibi MohammadCorresponding author Department of Civil Engineering, Ferdowsi University of Mashhad, Iran

Rainfall is one of the most important components of the hydrological cycle. The importance of rainfall in arid and semi-arid regions is more apparent. Due to the important role of rainfall trend assessment in the proper management of water resources, in the present study, Khorasan Razavi province, the second-most populous province of Iran located in the northeast of the country, for this purpose was studied. Currently, this region is facing water shortage problems. In this study, the non-parametric Mann-Kendall method was used to evaluate the annual rainfall trend over a thirty-year period from 1989 to 2019. On the other hand, Sen's slope estimator method was used to determine the magnitude of the rainfall trend in the studied synoptic and rain gauge stations. The results showed that the root of water shortage problems is not due to drastic changes in rainfall. Therefore, water shortage problems in Khorasan Razavi province are mainly due to a lack of proper management (i.e., mismanagement). The present study, by examining the rainfall trend using an appropriate framework, tried to take an effective step towards improving the management of water resources in the northeast of Iran.

Dolutegravir: Pharmacokinetics and Pregnancy Profile

Mar 2022
Bereda GudisaCorresponding author Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia

Dolutegravir suppresses this integration enzyme, so human immune virus can’t create every greater copies of itself, thus ‘’integrase inhibitor.’’ Dolutegravir is hastily absorbed pursuing oral administration. The median maximum plasma concentration is reached 1.5–2.5 hours after oral uptake with a mean half-life of 12–15 hours, rendering feasible for once-daily dosing without the need for pharmacological boosting. The terminal half-life is about 14 hours. The apparent oral clearance is about 1 liter/hour. Fifty three percent of the total oral dose of dolutegravir is excreted unchanged in the feces, thirty two percent through urine as glucuronide (eighteen percent) or alkylated product (three point five percent), and other organic conjugated products sequencing from phase II liver metabolisms. Dolutegravir’s categorized as pregnancy category B (no confirmation of pitfall in humans) means either animal-reproduction inquests have not substantiated a fetal peril but there are no restrained inquests in pregnant women or animal-reproduction inquests have reveal an adverse effect (distinctive than a de-escalate in fertility) that was not inveterate in restrained inquests in women in the first trimester (and there is no confirmation of a pitfall in later trimesters) or there is survey in animal that revealed the medication is safe in pregnant animal, but there is no fetal pitfall confirmation in pregnant women.Antiviral Pregnancy Registry (APR) revealed that as of January 2017, pregnancy outcomes and birth defects were analyzed from 142 pregnancies with reported exposure to DTG during pregnancy. There were 128 live births reported (3 terminations, 11 miscarriages, no stillbirths). Only 4 (3.0%) reported birth defects, which is similar to the expected rate of birth defects in the general population. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPIC) displayed that as of July 2017, 101 pregnancies with exposure to DTG had been identified with 84 birth outcomes. Rates of preterm delivery and “small for gestational age” were identical to outcomes reported from women on alternative regimens (standard of care in the United Kingdom of Great Britain and Northern Ireland).

Human Psychology Open Access

Perspectives of Workplace Incivility and Nurses Intent to Quit: Investigations Examined

Mar 2022 DOI 10.14302/issn.2644-1101.jhp-21-4037
Monique J. Grant CokeCorresponding author

The connection between the nurse employee’s apparent degree of work environment incivility and their expectation to stop their individual associations has been upheld by research for far over 10 years. Placed contentions have additionally analyzed a distinction in nurses' view of work environment incivility considering the kind of working environment (i.e., regardless of whether a public or private healthcare practice), considering the impression of existing working environment incivility and aim to stop employment, separately. The reason for such survey of writings is not just to decide the degree to which work environment incivility influences a nurses' plan to stop employment, yet more so to make for all viewpoints being additionally featured. Additional exploration on working environment incivility, remains continuous, with its related contributory elements, and the impacts on the examined relationships. New research on working environment incivility has critical ramifications for nurses, patients, healthcare services and associations were generally investigated 14569151718232427282943445868697172. Work environment incivility displays lack of respect, negligence or discourteousness that has formed into a combined issue, proved by irritating unfavorable consequences for human resources, and the adverse consequence on the association 78.

Nature Inspired Bargain Optimization Algorithm for Effective Interpretation of Geoelectrical Data

Jun 2021 DOI 10.14302/issn.2766-8681.jcsr-21-3796
Raj StanleyCorresponding author Department of Physics, Loyola College, Chennai, Tamil Nadu-India

Geoelectrical resistivity data collected from the ground contain lot of noises and errors. It requires efficient algorithm to reduce the errors to make an actual inversion models. Though different algorithm can be applied, nature inspired algorithm is more potential in inverting geoelectrical data in an elegant and comprehensive way. Bargain Optimization (BO) algorithm is framed on the concept of bargaining things to purchase for needs. In general, effective bargaining results in more profit and leads to loss when it fails. In this research work, Bargain Optimization algorithm is applied to invert geoelectrical data and the effective bargaining will take time to process and to obtain the required model. The input data is AB/2, apparent resistivity data and the inverted model through BO algorithm is successfully matched with the available litholog section of the study area. The output graphs have profit/loss bar graph, which reveals the status of bargaining during a particular number of epochs.

A Systematic Review of the Antimony Content of the Normal Human Prostate Gland

Dec 2020 DOI 10.14302/issn.2372-6601.jhor-20-3673
Zaichick VladimirCorresponding author Prof., Dr. Vladimir Zaichick, Medical Radiological Research Centre, Korolyev St. 4, Obninsk 249036, Russia.

The prostate gland is subject to various disorders. The etiology and pathogenesis of these diseases remain not well understood. Moreover, despite technological advancements, the differential diagnosis of prostate disorders has become progressively more complex and controversial. It was suggested that the antimony (Sb) level in prostatic tissue plays an important role in prostatic carcinogenesis and its measurement may be useful as a cancer biomarker. These suggestions promoted more detailed studies of the Sb content in the prostatic tissue of healthy subjects. The present study evaluated by systematic analysis the published data for Sb content analyzed in prostatic tissue of “normal” glands. This evaluation reviewed 1998 studies, all of which were published in the years from 1921 to 2020 and were located by searching the databases PubMed, Scopus, ELSEVIER-EMBASE, Cochrane Library, and the Web of Science. The articles were analyzed and “Median of Means” and “Range of Means” were used to examine heterogeneity of the measured Sb content in prostates of apparently healthy men. The objective analysis was performed on data from the 23 studies, which included 1173 subjects. It was found that the range of means of prostatic Sb content reported in the literature for “normal” gland varies widely from 0.0066 mg/kg to 0.071 mg/kg with median of means 0.0085 mg/kg on a wet mass basis. Because of small sample size and high data heterogeneity, we recommend other primary studies be performed.

Growth Performance of Heteroclarias Juveniles Fed Graded Levels of Autoclaved Castor Seed (Ricinus communis L.) Cake Based Diets

Jun 2020 DOI 10.14302/issn.2691-6622.ijar-20-3312
I. A AdebayoCorresponding author Department of Fisheries and Aquaculture, Ekiti State University, Ado-Ekiti, Nigeria

An 84 day feeding trial was conducted on the juveniles (42.51±0.09g) of hybrid catfish, Heteroclarias, in order to evaluate the nutritional potential of 30 minutes autoclaved castor seed cake isonitrogenous (40% crude protein) and isocaloric (3212Kcal/Kg) diets replacing soybean meal at 0, 12.5, 25, 37.5 and 50%, the diets being designated D1, D2, D3, D4 and D5 respectively. Prior to this, the castor seeds (Ricinus communis L.), ZiboCastor No. 3 variety, collected from Ado-Ekiti metropolis, Nigeria were subjected to 0, 20, 30 and 40 minutes autoclaved at 121oC, dehauled, grounded, oil extracted to form cake, then the proximate and antinutrients analysis were carried out. The preliminary tests on the seeds revealed 30 minutes level of autoclaved seeds was the best. The growth performance result showed that there were significant differences (p<0.05) in the mean weight gain (MWG), specific growth rate (SGR), feed conversion ratio (FCR), protein efficiency ratio (PER) and apparent net protein utilization (NPU) among the various diet levels with the progressive decline in the values of each parameter (except FCR that showed progressive increment) along the trend of increment of castor seed cake inclusion (D1, 0%; D2, 12.5%; D3, 25%; D4, 37.5% and D5, 50%). The survival rate followed the same trend of declination with the highest percentage recorded for D1 (93.33±6.67%), followed by D2 (83.33±3.33%), D3 (76.57±3.33%), D4 (66.67±3.33%) and D5 (60.00±5.77%) respectively. Hence the best growth performance and nutrient utilization was shown in D1 (control) followed by D2. It is therefore recommended that autoclaved castor seed cake at 121oC be included at not more than 12.5% inclusion level to reduce cost of feed without necessarily compromising fish growth rate.

Agronomy Research Open Access

Assessment of Ocimum basilicum as Potentially Fruit Flies Attractant

Apr 2020 DOI 10.14302/issn.2639-3166.jar-20-3250
H. M. Adam AbubakerCorresponding author Department of Crop Science, College of Agriculture, University of Bahri, Khartoum North, Sudan

The Basil plant (Ocimumbasilicum L) is an annual herb; belongs to family Lamiaceae. It is found to be an important source for Methyl Eugenol (ME), the fruit flies attractant. This study was carried out at Shendi area with main objective to assess the amount of ME extracted from Ocimumbasilicumplant to evaluate its potentiality as fruit fly attractant. Plants of basil were grown till to maturity, then the differential harvest of leaves, flower and seeds were chemically investigated for volatilome. Five basil formulations (paste and powder of leaves, paste and powder of flowers, isolated ME from basil oil) were used for trapping potential of Bactrocera spp in mango orchards, as compared to the synthetic ME. The oil was extracted using Soxhlet apparatus, steam and water distillation, and analyzed using GCMS. The results revealed that highest extracted oil percentages was obtained from flowers, leaves, seed and stem were 5.75%, 3.03%, 0.02% and 0.21% respectively. Moreover, the basil traps catch was found to be lower compared with that of the control traps. Furthermore, when extracted ME from basil plant was compared with the standard synthetic, it gave lower catch fruit flies numbers, but the difference was not significant (>0.05). In conclusion, the basil raw derivates are confirmed not to be attractive for flies but the oil distillable from the leaves could be in force of its attractant ME contents and insecticide potency.

RESinvANFIS v1.0 - A Versatile MATLAB Tool for Inverting Geoelectrical Resistivity Sounding Data using Neuro Fuzzy Technique

Apr 2020
Stanley Raj A.Corresponding author Department of Physics, Loyola College, Chennai, Tamilnadu- 600034, India.

Geoelectrical resistivity data is used for estimating the subsurface features of earth. It is very difficult to estimate the depth and true resistivity analytically, therefore many mathematical models approximates the result. The approximation relies on many parameters as the heterogenous model of earth is difficult to map. Conventional interpretation algorithm mostly uses the forward modelling technique which is limited for different lithologies. Here we presented ResinvANFIS v1.0 software platform to invert any type (A, Q, K, H or any mixed data types) of resistivity data having AB/2 and apparent resistivity data as input. This kind of generalised platform has not been done elsewhere to invert data directly using soft computing approach.

Using Prostatic Fluid Levels of Zinc to Bromine Concentration Ratio in Non-Invasive and Highly Accurate Screening for Prostate Cancer

Dec 2019 DOI 10.14302/issn.2372-6601.jhor-19-3094
Zaichick VladimirCorresponding author Radionuclide Diagnostics Department, Medical Radiological Research Centre, Obninsk, 249036, Russia.

Prostate specific antigen (PSA) does not provide the high reliability and precision that is required for an accurate screening for prostate cancer (PCa). The aim of our study was to search for a simple, rapid, direct, preferably non-invasive, and highly accurate biomarker and procedure for the screening for PCa. For this purpose the levels of bromine (Br) and zinc (Zn) were prospectively evaluated in expressed prostatic fluid (EPF). Also Zn/Br concentration ratio was calculated for EPF samples, obtained from 38 apparently healthy males and from 33, 51, and 24 patients with chronic prostatitis (CP), benign prostatic hyperplasia (BPH) and PCa, respectively. Measurements were performed using an application of energy dispersive X-ray fluorescent (EDXRF) microanalysis developed by us. It was found that in the EPF of cancerous prostates the levels of Zn and Zn/Br were significantly lower in comparison with those in the EPF of normal, inflamed, and hyperplastic prostates. It was shown that “Sensitivity”, “Specificity” and “Accuracy” of PCa identification using the Zn and Zn/Br levels in the EPF samples were all significantly higher than those resulting from of PSA tests in blood serum. It was concluded that the Zn and Zn/Br levels in EPF, obtained by EDXRF, is a fast, reliable, and non-invasive diagnostic tool that can be successfully used by local, non-urologist physicians at the point-of-care to provide a highly effective PCa screening and as an additional confirmatory test before a prostate gland biopsy.

Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease

Nov 2019 DOI 10.14302/issn.2574-4526.jddd-19-3063
I Alvarez-Leite JacquelineCorresponding author Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerias, Brazil.

Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.

Splanchnic Aneurysms & Possible Etiology

Aug 2019 DOI 10.14302/issn.2574-4526.jddd-19-2963
J. Demos NicholasCorresponding author Professor of Surgery, Rutgers Biomedical and Health Sciences, 65 Bergen St, Newark, NJ 07103

Four cases are reported with splanchnic aneurysms of the branches of the main arteries. Three of the cases presented as emergencies. Possible rupture was present in Case 2 and true rupture in Case 4. The etiology of Cases 1 and 2 may have been a floxacin antibiotics, Table 1. This report is the first clinical chronological association of the antibiotics and arterial and aortic pathology. This association was supported by nationwide research by Pasternak, 11. Detailed experimental work done on mice showed connective tissue fragmentation and arterial cell injury. Apparently, the above antibiotic induced mitochondrial DNA damage and dysfunction, 9.

Age-Dependence of Some Trace Element Concentrations and their Ratios in Human Prostatic Fluid

Jul 2019 DOI 10.14302/issn.2474-7785.jarh-19-2910
Zaichick VladimirCorresponding author Radionuclide Diagnostics Department, Medical Radiological Research Centre, Obninsk, 249036, Russia.

The effect of age on Br, Fe, Rb, Sr, and Zn concentrations as well as on Zn/Br, Zn/Fe, Zn/Rb, and Zn/Sr content ratios in human prostatic fluid was investigated by 109Cd radionuclide-induced energy dispersive X-ray fluorescent microanalysis. Specimens of expressed prostatic fluid were obtained from 51 men (mean age 51 years, range 18-82 years) with apparently normal prostates using standard rectal massage procedure. Mean values (M ± SΕΜ) for concentration of trace elements (mg·L-1) in human prostate fluid were: Br 3.62±0.58, Fe 9.04±1.21, Rb 1.10±0.08, Sr 1.19±0.14, and Zn 573±28. Mean values for ratios of trace elements in human prostate fluid were: Zn/Br 523±103, Zn/Fe 105±16, Zn/Rb 661±63, and Zn/Sr 719±95. An age-related increase in Zn content and decrease in Br and Fe concentration was found. Moreover, the strongly pronounced increase in Zn/Br and Zn/Fe ratios was also observed.

L162v Polymorphism of Par-Α Gene, A603g Polymorphism of Tissue Factor Gene and Risk of Coronary Heart Disease in Russian Population

Jun 2019 DOI 10.14302/issn.2374-9431.jbd-19-2788
Sergeeva E.G.Corresponding author First Pavlov State Medical University of St. Petersburg

Purpose The goal of this study is to determine the association of L162V polymorphism of PPAR-alpha gene, A603G polymorphism of tissue factor gene and the risk of coronary heart disease development in Russian population.   Materials and Methods A clinical and genetic study of 414 patients with CHD and 220 people of comparable age without CHD which amounted to a control group was performed. L162L and L162V genotypes of L162V polymorphism of PPAR-α gene, A603A, A603G and G603G genotypes of A603G polymorphism of tissue factor gene were determined by polymerase chain reaction followed by restriction analysis. Results A carriage of L162V genotype and V allele of PPAR-α gene was associated with an increase risk of CHD in 2,13 times (L162V genotype) and in 2,21 times (V allele), with an increase in risk of CHD before the age of 45 years in 4,68 times (L162V genotype) and in 3,88 times (V allele). Significantly higher in patients with CHD compared with the general population and in patients with a carriage of G603G genotype and G allele of tissue factor gene was associated with the increase of CHD risk in 2,68 times (G603G genotype) and in 4,37 times (G allele), occurred more frequently in patients with debut of disease at age of 45 years and younger. The level of tissue factor was significantly higher in patients with CHD – carriers G603G genotype compared with carriers A603A genotype (217,9±15,2 pg/ml and 152,6±30,4 pg/ml, respectively, p=0,04). A carriage of the combination of L162V and G603G genotypes was associated with an increased risk of CHD in 3,04 times. Conclusion A carriage of V allele of L162V polymorphism of PPAR-α gene and G allele of A603G polymorphism of tissue factor gene, as well as their pair combination are associated with an increased CHD risk, especially at age 45 years or less.

Zoological Research Open Access

Effect of Graded Levels of Spirulina (Arthropsira platensis) on Feed Intake and in vivo Digestibility of Trypsacum laxum in Guinea Pig (Cavia Porcellus L)

Apr 2019 DOI 10.14302/issn.2694-2275.jzr-19-2695
Miégoué EmileCorresponding author University of Dschang, Faculty of Agronomy and Agricultural Sciences, Department of Animal Production Animal Nutrition and production Research Unit B.P. 188 Dschang, Cameroun.

The intake and in vivo digestibility of Trypsacumlaxum in guinea pigs according to the graded level of spirulina was evaluated in Cameroon. 20 animals aged of 6 months with an average weight of 450 ± 50 g were randomly divided into 4 equivalent groups. Each group received T. laxum and 40g of compound feed containing 0% (TS0), 2% (TS2), 4% (TS4), and 6% (TS6) of spirulina. Feed intake was the different between the left over and the quantity served. The sample of T. laxum and those of each diet as well as feces were collected and analyzed for the apparent digestibility of each nutrient. Animals were weighed at the beginning and at the end of each period of the test to determine the body weight gain. This study showed that the average daily intake of dry matter (DM) for TS0, TS2, TS4 and TS6 was 74.39 ± 2.98, 78.66 ± 3.14, 83.89 ± 4.28 and 77.76 ± 4.40 g/head/day. The highest apparent digestibility coefficients of different nutrients were obtained with animals fed TS6 group while the lowest were observed in TS0.The apparent digestibility coefficient of dry matter (DM), organic matter (OM) and crude protein (CP) of the supplemented group were statistically higher than those of the control diet. Animals’ weight performances were statistically comparable between treatments. Thus, the combination of T. laxum with concentrated feed containing spirulina can be recommended for guinea-pigs, but the level of incorporation may not exceed 4% of its daily ration.

Antioxidant Activity Open Access

Purification and Characterization of Xanthine Oxidase from Liver of the Sheep (Ovis Aries)

Mar 2019 DOI 10.14302/issn.2471-2140.jaa-19-2699
M.M. Masoud HassanCorresponding author Molecular Biology Department, National Research Centre, El-Tahrir st., Dokki, Giza, Egypt.

Xanthine oxidase is a commercially important enzyme with wide area of medical applications to develop diagnostic kits. Xanthine oxidase was extracted, purified and characterized from sheep liver (SLXO). The purification procedure involved acetone precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 columns. The sheep liver xanthine oxidase was homogeneously purified 31.8 folds with 3.5 U/mg specific activity and 24.1% recovery. SLXO native molecular weight was 150 kDa and on SDS-PAGE appeared as single major band of 75 kDa representing a homodimer protein. Isoelectric focusing of the purified SLXO resolved into two closely related isoforms with pI values of 5.6 and 5.8. The apparent Km for xanthine oxidase at optimum pH 7.6 was found to be 0.9 mM xanthine. FeCl2 and NiCl2 increased the activity of SLXO, while CuCl2 and ZnCl2 were found to be potent inhibitors of the purified enzyme. Allopurinol inhibits SLXO competitively with one binding site on the purified molecule and Ki value of 0.06 mM.

Agronomy Research Open Access

Rice Yield Advances Under Precision Agriculture: a Farm Lesson

Mar 2019 DOI 10.14302/issn.2639-3166.jar-19-2691
Masoero GiorgioCorresponding author Accademia di Agricoltura di Torino, Italy

In precision agriculture (PA) fertilizing, based on soil testing, production maps and crop nitrogen (N) demand, is the key to maximizing yields and tempering fertilizer costs. A trend study has considered the output / input relationships performed on a farm that has progressively adapted to PA procedures over two decades. The evolutions of the variability parameters of yield, comprising the repeatability coefficient of repeated plots, the vegetative vigour (NDRE) at the panicle initiation (pi) stage, and the nitrogen utilization efficiency (NUE) were monitored and compared by means of mixed linear models over a six-year period, after the variable nitrogen (N) fertilization rate (VNFR) had been enlarged to the whole 230 ha of one farm. At pi key fertilization stage, a corrective dose was applied by tacking the correlation between Npi and the measured NDRE in strong negative mode. The evolution of the yield, for the 2012-2017 interval, based on 1165 ha-1 parcel-data, showed a significant yearly increase of 2.3% more than the regional trend (+0.5%). The variability parameters of the yield, that is, the standard deviation (+7.3%), range (+7.1%), coefficient of variation (+5.4%) and maximum (+2.1%) were enhanced over the years, but the minimum remained stable. The repeatability of the parcel yield generally appeared low (r = +0.31), but it tended to increase by 8.3% year-1 (P = 0.018). At the same time, the vegetational vigour also showed significant increases of the NDRE means (+3.0%) as well as of the maximum (+0.8%), but also large oscillations in the standard deviation and in the coefficient of variation. No significant regression of the NDRE on the coefficient of variation of the yield was established. The favorable increase in yield was found to be independent of the distributed N-total. A strong negative correlation (imposed) between N-pi and NDRE (-0.90) and a negative correlation with production were observed for a sample field (but in the area of maximum production). It is recommended that a partial correlation between Yield and N-tot should be considered in the I /O features for a parity of NDRE, which apparently decreases the negativity of the relationship. In short: with the same total input of N, the PA increased the yield, but also its variability – and it did not reduce the variability as predicted by the theory - by strengthening the repeatability. This is an evidence that in many of the parcels with minimum yield the limiting factors cannot  be referred to the N availability.

Could Painful Experience in the Neonatal Period Trigger Persistent Anxiety-Like Behavior?

Mar 2019
Paula Sassoli Fazan ValeriaCorresponding author Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Av. Bandeirantes 3900, Ribeirao Preto-SP, Brazil

We used a behavioral test to investigate long-term consequences of neonatal noxious stimulus in the anxiety-like behavior and describe differences between males and females. Male and female Wistar rats were submitted to either tactile (control groups) or noxious stimulus (pain groups) since birth, for 15 days and were followed up to 6 months of life. Experiments were performed on days 15, 30, 90 and 180 after birth. Rats of different groups, ages and genders were exposed only once to the elevated plus-maze (EPM), an apparatus largely used to detect anxiety-related behaviors in rats. For the open arms of the EPM, control animals showed an increase in the number of entries from 15 to 30 days of age followed by a decrease of this number at older ages. The comparison between treatments (control and pain) showed, for males, a reduced number of entries in the open arms in the pain group at 15 and 30 days and the opposite situation at 180 days. No differences were found between pain and control groups in females. Our results are in agreement with the literature that shows sex-dependent changes following chronic stress; stress being anxiolytic in males and anxiogenic in females. We point to the fact that acute painful stimulus in the neonatal period caused persistent changes in anxiety-like behavior in the adult life, independently of previously described intrinsic gender differences on memory, task performance, attention bias or other behaviors.

Dose Body Mass Index (BMI) Fit to Muscular Individual?

Dec 2018 DOI 10.14302/issn.2578-8590.ipj-18-2532
Habibzadeh NasimCorresponding author PhD in Sport Science, Department of Sport Science, Teesside University, UK

Body mass index (BMI) seemingly is an important scale for the body types determination in individual with different ethnicity. Accordingly, individual with BMI< 18.5 are classified as slim or underweight and people with BMI between 18.5 -24.9 are called normal body types. Subsequently, those individual with BMI between 25-29.9 are categorized as overweight and people with BMI > 30 are classified as obese people. Nonetheless, important question is where the muscular individual are located in this BMI scale ? Macular induvial also called overweight or obese in BMI scale which can create kind of confusion for induvial because the might try to lose weight whilst they do not actually need it. Thus ,it seems BMI measure is not sensible measure for muscular induvial as otherwise the can be at risk of health problems in various ways. Uses of the another apparatus such an ordinary weight scale or computational devices which could estimate the body type according to the BMI more accurately can be helpful.

Is the Measles Virus Indeed Involved in Carcinogenesis? – Commentary

Aug 2018 DOI 10.14302/issn.2641-9181.ijnr-18-2195
Benharroch DanielCorresponding author Independent Physician, Department of Pathology, Soroka University Medical Centre and Faculty of health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Objectives: An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts. Methodology: It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and in situ hybridization evidence of measles virus RNA. Key Results: At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments. Major Conclusion: As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.

Validated Analytical Spectrofluorimetric Method for Quantitation of Diphenhydramine HCl in Commercial Dosage Forms

Aug 2018 DOI 10.14302/issn.2377-2549.jndc-18-2220
Najmul Hejaz Azmi SyedCorresponding author Department of Applied Sciences, Chemistry Section, Higher College of Technology, P. O. Box 74, Al-Khuwair-133, Muscat, Sultanate of Oman

Diphenhydramine HClis a weakly fluorescent drug having tertiary amine group forming ion pair complex with eosin Y in dichloromethane at pH 5 in disodium hydrogen phosphate-citric acid buffer solution. The complex formation was the basis for the development of new analytical method for determination of active diphenhydramine in pharmaceutical formulations. The stoichiometric ratio between diphenhydramine and eosin Y was studied by mole ratio method and found to be 2:1. The ion-pair complex showed maximum fluorescence emission intensity at 554 nm with excitation at 259 nm. The linear dynamic range was obtained in the concentration range of 2-22 µg mL-1 with a linear equation of FI = 0.361 + 13.675 C. The apparent Gibb’s free energy (ΔGº) was calculated and found to be -80.783 KJ mol-1, confirmed the feasibility of the reaction. The proposed method was successfully applied to the determination of diphenhydramine HCl in pharmaceutical formulations and in good agreement with the reference method.

The Therapeutic Effect of Bilateral Alternating Stimulation Tactile Form Technology on the Stress Response

Feb 2018 DOI 10.14302/issn.2576-6694.jbbs-18-1887
S. Hageman NathanCorresponding author David Geffen School of Medicine at UCLA, Los Angeles, CA Corresponding Author

The application of bilateral alternating stimulation in tactile (BLAST) form technology, a non-invasive, somatosensory-based method, has been shown to modulate the electrical activity of brain networks that mediate the stress response, resulting in a stress-reducing effect in individuals with high reported levels of anxiety, such as post-traumatic stress disorder (PTSD). In this study, we examined archival data from a heterogeneous group of users (n = 1109) of BLAST technology via Touchpoints, a novel BLAST-based treatment modality, all of whom had high self-reported levels of stress and anxiety. Ratings of levels of emotional stress and bodily distress on a scale of 0 (no stress/distress) to 10 (worst stress/distress of one's life) before and after the application of Touchpoints for 30 seconds were entered into an app. Results showed a statistically significant reduction in the levels of both emotional stress and bodily distress, 62.26% and 50.502%, respectively, after 30 seconds of BLAST technology was applied. This demonstrates a clear benefit of BLAST on the stress response, reducing both emotional stress and disturbing body sensations. Recent work examining EEG changes after BLAST technology is applied suggests that BLAST may reduce sympathetic activation by reducing the electrical activity of key areas of the salience network. Further work will more precisely characterize the effects of BLAST, its potential clinical uses, and the mechanisms of actions behind it’s apparent stress-reducing effects.

Predictive Value of Some Central Obesity Anthropometric Indicators to Metabolic Risk Factors in Syrian Adolescents

Jan 2018 DOI 10.14302/issn.2576-6694.jbbs-17-1850
Al-Bachir MahfouzCorresponding author Department of Radiation Technology, Atomic Energy Commission of Syria, Damascus, Syrian Arab Republic.

Obesity has become a serious health issue worldwide. There is much evidence that obesity among adolescents contributed to worsening blood biochemical profile that leads to development of many non-communicable diseases. Therefore, the aim of this study was to evaluate the predictive value of some central obesity anthropometric indicators to metabolic risk factors in the Syrian male adolescents. A cross-sectional study of a randomly selected sample of 2064 apparently healthy Syrian males’ adolescents from Damascus city, Syria, aged 18 to 19 years was performed. Waist circumference (WC) and hip circumference (HC) were measured, and waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR) were calculated. Blood pressure (BP) was also measured. Serum fasting blood sugar (FBS), triglyceride (TG), low-density lipoprotein cholesterol(LDL-C), total cholesterol (Chol) were determined. The metabolic risk factors components were defined according to the national criterion. A receiver operating characteristics (ROC) curves were drawn to determine appropriate cut-off points of the WC, HC, WHpR and WHtR for defining the performance of these measurements as predictors of metabolic risk factors. The obtained data showed that BP and overall concentrations of TG, Chol and TG/HDL were significantly (p<0.05) increased with increasing WC, HC, WHpR and WHtR values. Based on ROC calculation for the measured anthropometric indicators and some metabolic syndrome (MetS) risk factors, the best WC HC, WHpR, WHtR cut-offs values were ranged between 73.15 - 79.90 cm, 93.75 - 101.10 cm, 0.80 - 0.81, and 0.43 and 0.47, respectively. These cut-off values were lower than the values recommended by the WHO. In conclusion: A significant association between the studied anthropometric indicators and the MetS components has been demonstrated. The best cut-offs of these indicators were defined. These cut-off values were lower than the values recommended by the WHO. Our results indicating that WC, WHpR and WHtR could be better predictors of MetS risk factors in Syrian adolescents.

Immunization Open Access

Advanced Virological And Clinicopathological Studies On Cattle Suffering From Foot And Mouth Disease Virus

Sep 2017 DOI 10.14302/issn.2577-137X.ji-17-1736
Ahmed Kamal SamiaCorresponding author Animal Health Research Institute, Dokki, Giza, Egypt

Some strains of Foot and mouth disease virus (FMDV) are endemic in Egypt. The present study was performed on cattle and buffaloes (ages: 3 months up to 1.5 years old, of years 2015 and 2016), which were suffering foot and mouth disease (FMD). Sera and tissues samples were tested by different techniques including serum and virus neutralization tests (SNT, VNT), virus isolation and identification by tissue culture methods, Enzyme linked immune-Sorbent Assays (ELISA); and by the pathological and hematology techniques. The results showed the predominance of FMDV serotype O with the presence of serotypes SAT2 and A. The results showed the pathologic picture of FMD was similar regardless its specific subtypes, as apparently the studied strains produces same pathological and hematological changes. Microscopic examination reveals severe hydropic degenerations and necrosis in most affected organs, accompanied by significant changes in blood parameters which indicate severity and direct effects of FMDV on the hematopoietic system. These findings indicates the mode of pathogenesis of FMD virus in its way to exhibits the characteristic symptoms of illness. However, the investigation showed the presence of FMDV type O, A and SAT2 in the studied areas of delta governorates. It is important to focus on producing of vaccines which have only these serotypes as solution to get rid of the endemic behavior of FMDV in delta of Egypt.

Bioinformatic Analysis of Coronary Disease Associated SNPs and Genes to Identify Proteins Potentially Involved in the Pathogenesis of Atherosclerosis

Mar 2017 DOI 10.14302/issn.2326-0793.jpgr-17-1447
D. Howard TimothyCorresponding author Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

Factors that contribute to the onset of atherosclerosis may be elucidated by bioinformatic techniques applied to multiple sources of genomic and proteomic data. The results of genome wide association studies, such as the CardioGramPlusC4D study, expression data, such as that available from expression quantitative trait loci (eQTL) databases, along with protein interaction and pathway data available in Ingenuity Pathway Analysis (IPA), constitute a substantial set of data amenable to bioinformatics analysis. This study used bioinformatic analyses of recent genome wide association data to identify a seed set of genes likely associated with atherosclerosis. The set was expanded to include protein interaction candidates to create a network of proteins possibly influencing the onset and progression of atherosclerosis. Local average connectivity (LAC), eigenvector centrality, and betweenness metrics were calculated for the interaction network to identify top gene and protein candidates for a better understanding of the atherosclerotic disease process. The top ranking genes included some known to be involved with cardiovascular disease (APOA1, APOA5, APOB, APOC1, APOC2, APOE, CDKN1A, CXCL12, SCARB1, SMARCA4 and TERT), and others that are less obvious and require further investigation (TP53, MYC, PPARG, YWHAQ, RB1, AR, ESR1, EGFR, UBC and YWHAZ). Collectively these data help define a more focused set of genes that likely play a pivotal role in the pathogenesis of atherosclerosis and are therefore natural targets for novel therapeutic interventions.

Synthesis and Assessment of a New Tetrahydrogeraniol Derivative as Penetration Enhancer for Transdermal Drug Delivery

Oct 2016 DOI 10.14302/issn.2572-5424.jgm-16-1170
Majid Khan GulCorresponding author Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan

Background: Skin is one the most important sites for administration of drugs to obtain desired pharmacological effects either locally or through systemic bioavailability; and this has placed the transdermal route of drug delivery as an attractive and as one of the most innovative areas for conducting drug delivery research. However the stratum corneum in skin creates hurdles and acts as significant barrier for the permeation of drugs through skin. Penetration enhancers play a pivotal role to overcome such barriers and help enhance the permeation of drug through skin. However, penetration enhancement technology is challenging development and needs to be properly and skillfully addressed. Objective: The present investigation aimed to study the penetration enhancing effect of a newly synthesized alcohol derivative of an acyclic monoterpene (Tetrahydrogeraniol-THG). Methodology: The new derivative, 5,9-Dimethyl-1-Decanol (DIMDOL), has been synthesized by a chemical reaction of the THG with Grignard reagent and ethylene oxide. Permeation enhancing effect of the synthesized derivative was explored for better transdermal penetration of the two model drugs viz. tramadol hydrochloride and 5-fluorouracil (5-FU) through the excised rat skin by conducting in-vitro permeation experiments employing Franz diffusion cells apparatus. The standard enhancers Azone and THG were used to compare penetration enhancing effect of the enhancers. Results: It was revealed that DIMDOL could effectively enhance the permeability of both the drugs by 18.60 and 73.19 folds across the skin used with a lag time of 3.35 and 1.20 h, respectively. The newly synthesized derivative was found to significantly increase the partition coefficient and diffusion coefficient values. Conclusion: The results obtained suggest that DIMDOL can more effectively enhance the permeation of these model drugs, expectedly by affecting the stratum corneum and interacting with both lipid-rich layers and keratin-rich layers of the excised rat skin.

A study on the association of ACE i/D gene polymorphism, Obesity, Blood pressure and susceptibility of type 2 diabetes mellitus among the Kurmis of West Bengal, India.

Jun 2016
Ratan Bandyopadhyay ArupCorresponding author Department of Anthropology, University College of Science, Technology & Agriculture, University of Calcutta, India

Earlier studies reported significant association of obesity, hypertension and Type2 Diabetes Mellitus (T2DM). Genetic and many disease-associated alleles have been identified through GWAS and applied to T2DM and indicated roles of renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been well documented. Angiotensin converting enzyme (ACE) gene catalyzes the conversion of angiotensin I to angiotensin II and also inactive the vasodilatation and hence renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been reported. To best of the knowledge we are reporting for the first time regarding association of ACE gene polymorphism with body composition, physiological and metabolic variables among any endogamous ethnic group (Kurmis) from of West Bengal, Eastern India. To achieve the purpose, total 197 (male 99 and female 98) randomly selected apparently healthy unrelated adult individuals of Kurmi population of Purulia District, West Bengal, India were incorporated in the present study. Anthropometric variables, physiological variables (blood pressure) and metabolic variables (PP blood sugar) have been collected using standard techniques. Extracted genomic DNA was PCR amplified and genotyped to understand ACE gene I/D polymorphism. The result demonstrated significant (p<0.05) sexual dimorphism in PBF. MAP and PP blood sugar found to be in normal range among the Kurmis. ACE gene polymorphism showed no deletion of the Kurmis and hence, only the prevalence of ACE II (insertion-Insertion) genotype has been noticed. The present study vindicated on the basis of body composition in terms of fat patterning, physiological and metabolic variables and ACE gene polymorphism that there is very low or no risk of T2DM among the Kurmis of West Bengal, India.

Early Glycine Supplementation Re-Establishes Adrenal Catecholamine Secretion in Hypothalamic Obesity Model in Rats but does not Affect Visceral Adiposity.

Jun 2015 DOI 10.14302/issn.2572-5424.jgm-14-604
Eliza Andreazzi AnaCorresponding author Laboratory of Physiology, Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora/MG - Brazil

Obesity is a worldwide epidemic that features a multifactorial syndrome characterized by a chronic positive energetic unbalance. Neonatal administration of monosodium L-glutamate (MSG) causes lesion on the arcuate nucleus of hypothalamus that led to development of obesity in the adult life in rodents characterized by a notorious accumulation of catecholamine in the adrenal medulla. The amino acid glycine induces catecholamine secretion of adrenal medulla. Thus, the objective of our work was to evaluate the possible effects of glycine administration in the MSG-obesity model in rats and investigate its impact on adrenal catecholamine medulla homeostasis. Male Wistar rats received MSG solution (4mg/g body weight) subcutaneously in the cervical area for 5 days after delivery, controls received saline solution. Animals were also divided in two groups, in which one received tap water added with glycine (0.1g/Kg) after weaning on 21st day until 90 days of life.Biometrical variables, visceral fat pads weight, total content and basal secretion of adrenal cathecolamine were evaluated. Glycine increased Lee index of all tested groups and had no effect on visceral adiposity. However, glycine treatment completely reestablished catecholamine total content and basal secretion of MSG-obese group. In conclusion, although glycine treatment apparently completely reestablishes catecholamine secretion homeostasis it is not sufficient to significant directly reduce visceral adiposity in MSG obesity model in rats.

The Pharmacist Knowledge and Computer Skills Towards E-Health. Results of A Survey among Italian Community Pharmacists

Jun 2014 DOI 10.14302/issn.2374-9431.jbd-13-330
Grappasonni IolandaCorresponding author University of Camerino. School of Pharmacy. Via Madonna delle Carceri,

Background: Health practitioners of different disciplines (physicians, paramedic personnel, pharmacists) should possess adequate ICT (Information and Communication Technology) skills and practical competence on these technologies. Pharmacy practice requires a relevant flow of information, collection and handling of which could be facilitated by ICT. The correct use of ICT requires a proper knowledge by professionals offering a public service. The purpose of this paper was to assess basic informatics background and computer uses in pharmacists practicing in Italy, with the aim to identify educational interventions for increasing their informatics abilities. Methods: A questionnaire was proposed to pharmacists working in Italian community pharmacies. The survey was articulated into 35 questions concerning computer basic knowledge, ICT facilities, computer skills, habits, and uses in pharmacy practice. Results: The questionnaire was completed by ~45% (No. 224) of responders, the 96.9% of which used computer. Only 7.8% of interviewed people employed e-mail to communicate with health authorities and less than 2% used it to be in contact with physicians or other health professionals. Less than 40% used ICT for training courses. The results revealed a relevant percentage (90.8%) of self-learners to computer use, while only 9.2% was trained by specific courses. Conclusion: Basic knowledge of community pharmacists on ICT technological infrastructure is quite low. Although pharmacists play an essential role in health services, they have apparently limited computer skills. This suggests the need of educational and training efforts for enlarging computer and ICT resources competent use in daily pharmacy practice.  

Factors that Influence Fenofibrate Effects on Cancer Cells

Mar 2014 DOI 10.14302/issn.2372-6601.jhor-13-362
A. Vlahopoulos SpirosCorresponding author Horemio Research Institute, First Department of Pediatrics, University of Athens Medical School, “Aghia Sophia” Children’s Hospital, Athens, Greece

A narrative review summarizes how fenofibrate influences cancer cell metabolism and proliferation. It reviews PPAR‑α–dependent and independent mechanisms, context‑specific effects, and implications for repurposing studies.

Effect of Nonionic Surfactants and HPMC F4M on the Development of Formulations of Neuro-EPO as a Neuroprotective Agent

Feb 2014 DOI 10.14302/issn.2328-0182.japst-13-206
C. García-Rodríguez J.Corresponding author Life Sciences and Nanosecurity, Scientific Advisor’s Office.

The purpose of this study was to investigate the effect of cremophor RH-40 and polysorbate 80 with hydroxypropyl methylcellulose (HPMC) F4M on the development of formulations of intranasal erythropoietin with low sialic acid content (Neuro-EPO) as a neuroprotective agent. Parameters such as pH, osmolality, apparent viscosity, and protein concentration were controlled for minimizing the differences between formulations. All Neuro-EPO formulations showed similar behaviour in the physicochemistry quality control. However significant differences between formulations were observed in the permanent unilateral ischemia model. The formulations and the vehicles containing cremophor RH-40 showed higher neurotoxicity levels than those containing polysorbate 80 as a nonionic surfactant. Formulations containing HPMC F4M at 0.6% as a bioadhesive polymer showed higher levels of survival and better neurological status than those without the polymer. The formulations with polysorbate 80 and HPMC F4M showed a higher index of survival, smaller incidence of clinical signs of stroke, and similar behavior in the learning and the memory to the false injured animals used as control. These findings suggest that the intranasal pathway constitutes a safe and alternative route of access of the Neuro-EPO to the brain.

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