Open Access Original Research Article

Acute and Subacute Toxicological Assessment of the Leaf Aqueous Extract of Eremomastax speciosa (Acanthaceae) in Wistar Rats

Gaël Tchokomeni Siwe, George Enonchong Enow-Orock, André Perfusion Amang, Christophe Mezui, Alain Bertrand Dongmo, Paul Vernyuy Tan

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-13
DOI: 10.9734/JAMPS/2015/18361

Aim: The present study was carried out to investigate the possible toxic effects of the leaf aqueous extract from Eremomastax speciosa and also to evaluate the acceptable safety level of this extract in Wistar rats.

Place and Duration of Study: Department of Animal Biology and Physiology, Faculty of Sciences of the University of Yaounde I, between September and December 2013.

Methodology: The acute assay used 9 female rats distributed into 3 groups of 3 rats each. A control group received distilled water and the two test groups received by oral route a unique dose of the extract at 2000 mg/kg with 48 hours interval. In the subacute assay, 60 rats of both sexes were distributed into 6 groups of 10 rats each (5 males and 5 females) and received the extract by oral route for 28 days consecutively. The tests groups received the extract at doses of 400, 800 and 1600 mg/kg. The controls and satellite test groups received, respectively, distilled water and extract at the dose of 1600 mg/kg. Anthropometric, hematological and biochemical parameters were measured and histological sections of liver, kidneys and lungs were realized.  

Results: The results showed no signs of toxicity such as general behavior change, mortality or change in gross appearance of internal organs even at high dose (2 g/kg). In subacute toxicity assay few modifications were observed in hematological and biochemical parameters. Histopathology showed the presence of disturbances at the dose of 800 and 1600 mg/kg particularly in the females.

Conclusion: The aqueous extract of the leaves of E. speciosa could be moderately toxic at high doses and adequate caution should be exercised in its use in ethnomedicine.

 

Open Access Original Research Article

Design of COX-1 Inhibitors Utilizing Class I Isosteres, Class II Isosteres, and Nonclassical Bioisosteres for Substituent Substitution on Proved Parent Structures

Ronald Bartzatt

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-15
DOI: 10.9734/JAMPS/2015/18954

Aims: To identify isosteres and bioisosteres suitable for substitution on the molecular scaffold of meclofenamic acid and tolfenamic acid. The compounds will be studied to determine drug-likeness and other properties.

Study Design: Isosteres and bioisosteres were selected and emplaced on the scaffold of meclofenamic acid and tolfenamic acid to ascertain drug-likeness outcome. Drug candidates were selected based on favorable drug-likeness.

Place and Duration of Study: Chemistry Department, University of Nebraska at Omaha, Omaha Nebraska from March 2015 to May 2015.

Methodology: Two non-steroidal anti-inflammatory drugs, meclofenamic acid and tolfenamic acid, are selected based on versatile isosteres and bioisosteres substitution. Placement of class I isosteres, class II isosteres, and nonclassical bioisosteres was accomplished using molecular modeling software. Physicochemical properties were determined and compared by numerical analysis and by pattern recognition. This approach is evaluated for success in generating drug-like compounds.

Results: Utilizing meclofenamic acid as parent compound, a total of 13 class I isosteres, five class II isosteres, and four non-classical bioisosteres were identified. For this group the Log P and polar surface area values ranged from 2.534 to 6.268 and 49.326 Angstroms2 to 101.372 Angstroms2, respectively. Utilizing tolfenamic acid as parent compound, a total of ten class I isosteres, five class II isosteres, and four non-classical bioisosteres were identified. For this group the range of Log P and polar surface area values were 1.904 to 5.408, and 37.299 Angstroms2 to 75.349 Angstroms2, respectively. Multiple regression analysis of properties produced equations useful for prediction of similar drugs for both groups.

Conclusion: Variations of physicochemical properties by isosteres (class I and class II) and bioisosteres, successfully produced 22 of meclofenamic acid based drug designs and 19 of tolfenamic acid based drug designs. All compounds were evaluated for drug-likeness and similarities by cluster analysis. New drug designs are needed for COX-1 inhibition.

 

Open Access Original Research Article

Clinical Use and Complications of Peripheral Venous Cannulae among Adult Patients in a Nigerian Tertiary Hospital, Benin City: A Pilot Study

S. Adewoyin Ademola, O. Ogunnowo Tolulope

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-8
DOI: 10.9734/JAMPS/2015/19223

Background: Peripheral venous catheterization is a common medical procedure among hospitalized patients. Its use is fraught with potential complications including thrombophlebitis and blood stream infections. This necessitates provision of appropriate local protocols, meticulous use and regular surveillance, particularly in developing nations like Nigeria. This study therefore evaluates the pattern of use, care practices and complications associated with peripheral venous cannulae (PVC) in a Nigerian teaching hospital.

Methods: Using an interviewer-administered questionnaire, relevant bio-, clinical and laboratory data were collected through an interview process and case file reviews. A total of 143 consenting adult patients on admission in the different medical and surgical wards were interviewed consecutively over a period of two months.

Results: A total of 79 (55.2%) subjects had in-situ PVC during admissions. Commonest indications for PVC insertions were administration of intravenous fluid therapy (74.7%), followed closely by intravenous antibiotics (68.4%). Catheter-related complications were observed in 53.2% of PVC insertions, with phlebitis being the commonest (46.8%), followed by infiltration (17.7%). Length of catheter indwell times was significantly associated with phlebitis (p = 0.017).

Conclusion: Authors recommend provision of local guidelines and protocols for PVC insertion and maintenance with emphasis on asepsis. There should be adequate information and proper documentation regarding PVC use, coupled with consistent surveillance and vigilance to detect complications promptly. Although, further studies are needed in this regard, routine maintenance PVC removal or replacement every 72 to 96 hours may be a better option in our locality.

 

Open Access Original Research Article

5HT1a Receptor Binding Affinities of a Series of Serotonin Transporter (SERT) Inhibitors and Related Thermodynamic Insights^

Gisella E. Alfonsino, Andrea Santagati, Livia Basile, Ettore Novellino, Corey Gaul, Carley Squires, Michael Braden, John M. Gerdes, Silvia Pérez Silanes, Salvatore Guccione, Keith K. Parker

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-12
DOI: 10.9734/JAMPS/2015/18917

Clinical depression encompasses a complex neurobiology involving multiple interacting systems. This intricate pathophysiology is, in part, correlated with dysfunction in serotonin (5HT) neurochemistry. The 5HT1a receptor (R) and SERT (serotonin transporter) components of this network are highly correlated to mood and anxiety regulation and difficulties in this regard in the realm of depression.

Aims: The current study was designed to develop a series of arylpiperazine derivatives ligands that are antagonists at both H5HT1aR and SERT.

Study Design:  Development of new chemotype antagonists at H5HT1aR and SERT.

Place and Duration of Study: University of Catania (Italy) and University of Montana, Missoula, Montana, May 2008 to June 2013.

Methodology: Chinese Hamster Ovary cells transfected with the gene for the Human (H) 5HT1a Receptor were cultured, and membranes containing the receptor were prepared for competition assays between the test compounds and the agonist, [3H]8-OH-DPAT. For thermodynamics, Ki's were determined at a series of temperatures from 0-35 degrees C. Further, membranes from rat brain were utilized for competition assays between the test compounds and the SERT inhibitor, [3H] paroxetine.

Results: Many of these substances show nanomolar affinities at H5HT1aR, and a number of the compounds also have high efficacy in inhibiting SERT. It is of note that some members of this series also substantially discriminate between binding at H5HT1aR and H5HT7R, a receptor studied with these compounds in previous work. Thermodynamic properties for the compound 4-[4-(3-benzo [b] thiophen-3-yl-3-oxopropylamino) piperidin-1-yl] benzonitrile (BTPN; compound15) are also reported.

Conclusions: There are a few of these compounds that excel in all three categories of H5HT1aR affinity, SERT inhibitory activity, and discriminatory binding capacity between the two receptors. Implications in the context of clinical needs in depression and other nervous systems disorders are discussed.

 

Open Access Original Research Article

A Pilot Study on the Association Between Trunk Hair Density and Insulin Resistance in Nonobese Turkish Men

Nilay Duman, Betül Aydın Buyruk

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-7
DOI: 10.9734/JAMPS/2015/19450

Aim: The association between insulin resistance and hirsutism in women is well studied.  However there is no previous data about association between insulin resistance and male body hair density. Thus, the aim of the present study is to evaluate association between insulin resistance and trunk hair density in nonobese Turkish men.

Study Design: This is a a cross-sectional, observational, pilot clinical study conducted with the approval of ethical review board.

Place and Duration of Study: Department of Internal Medicine and Dermatology, Afyonkarahisar State Hospital, between July 2014 and October 2014.

Methodology: The study included 58 nonobese Turkish men with same ethnicity, without a systemic disorder. The body mass index (BMI) was calculated, and total trunk hair density was evaluated with a scoring method for each participant. Laboratory investigations, including fasting blood glucose, insulin and serum lipid levels were performed. In each patient, insulin resistance was calculated as Homeostasis model assessment of insulin resistance (HOMA-IR).

Results: Mean age of the patients was 27.88±8.14 (range: 17-58). Total trunk hair score positively correlated with BMI (P = 0.001), fasting insulin levels (P = 0.021), HOMA-IR score (P = 0.019) and insulin resistance (P = 0.003). Especially, abdominal hair score correlated with insulin resistance (P = 0.003).

Conclusion: Total trunk hair score, especially abdominal hair score correlated positively with insulin resistance in nonobese Turkish men. Thus, evaluation of abdominal hair density may be a clinical method for risk assesment of insulin resistance in nonobese Turkish men.