DARU, Journal of Pharmaceutical Sciences
Volume:14 Issue: 4, Winter 2006

The aim of this study was to investigate the relationship between the intestinal absorption of structurally diverse model drugs across the rat intestinal mucosa and their molecular properties. Permeability coefficients for 13 compounds were determined in anaesthetized rats. Drug solution in phosphate buffered saline (PBS) was perfused through the intestinal segment with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. The permeability values ranged from 1.6×10-5 to 2 ×10-4 cm/sec for atenolol and ibuprofen respectively. Molecular properties of drugs including the number of hydrogen bond donors and acceptors, log P, logD, topological polar surface area and number of rotatable bonds were considered. The results indicated that compounds which meet 10 or fewer number of rotatable bonds and topological surface area equal to or less than 140 A◦ have a high probability of good intestinal permeability and fraction of dose which is absorbed in human. Moreover the results indicated that lower number of hydrogen bond counts and higher logD and logP values are associated with higher permeability and bioavailabilty of drugs. Therefore the experimental and computational methods could be used for the prediction of intestinal drug permeability.

The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-release vaginal tablets prepared by using six different retarding polymers and from two effervescent tablets prepared by using citric or adipic acid. The Carbomer–based formulations showed high initial viablility compared to those based on HPMC-LV, HPMC-HV, Polycarbophil and SCMC polymers which showed one log decrease in viable cells. All retarding polymers in slow release formulations presented a strong bacterial release at about 2 h except Carbomer polymers which showed to be poor bacterial releasers. Although effervescent formulations produced a quick bacterial release in comparison with polymer based slow-release tablets, they were less stable in cold storage. Due to the strong chelating characteristic of citric acid, the viability was quickly lost for aqueous medium of citric acid in comparison with adipic acid based effervescent tablets.

Chlorhexidine mouthwash has shown the highest antimicrobial effects in orthodontic patients, however, some complications have limited its widespread use. The goal of this study was to compare the antimicrobial effects of persica mouthwash with chlorhexidine in fixed orthodontics patients. Sixty patients (13-18 years old) on fixed orthodontic treatment, with desirable oral health were randomly divided into three equal groups of control, clorhexidine and persica. Patients were educated to properly use these mouthwashes. The control group was asked to wash their mouth with water twice a day. The numbers of streptococcus mutans colonies available in the elastic rings around the two bracket bases were determined in culture mediums before and immediately after a single application of water or mouthwashes and also following their daily uses for three weeks. The number of bacterial colonies then were compared at these three graps. The use of persica resulted in a significant (p<0.001) reduction in the number of streptococcus mutans colonies, albeit it was not as potent as chlorhexidine. Thirteen and fourty percent of patients using persica mouthwash experienced tooth discoloration and changes in taste respectively. The corresponding figures for chlorhexidine were 86% and 73% respectively. Significant reduction of streptococcus mutans colonies by persica as well as its lower tooth discoloration effects and unpleasant taste relative to chlorhexidine might give credence to the use of complementary herbal compounds in orthodontics patients.

Somatostatin receptor (sstr) scintigraphy with [111In diethylenetriaminepentaacetic acid]-octreotide ([111In-DTPA]-OC) has became a routine diagnostic procedure in oncology. However, it suffers from some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of 111In. In this study synthesis, conjugation and preclinical evaluation of two new freeze-dried kit formulation based on somatostatin analogues, Tyr3-Octreotide (TOC) and Tyr3-octreotate (TATE), designed for the labeling with 99mTc are described. After cleavage from the resin and preparation of the cyclized peptides, these compounds were conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) in solution. Radiolabeling of HYNIC peptide conjugates was performed at high specific activity using one-step kits formulation based on tricine and ethylenediamine-N,N′ -diacetic acid (EDDA) as co-ligands. Both, 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotide (HYNIC-TOC) and 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotate (HYNIC-TATE), showed a specific and high rate of internalization after 4 h in AR4-2J rat pancreatic tumor cells, (11.2±0.8 and 18.1±1.2 respectively). Biodistribution studies in AR4-2J tumor-bearing rats showed rapid clearance of both analogues from all sstr-negative tissues except the kidneys. The specific uptake in tumor and sstr-positive tissues especially pituitary, pancreas and adrenals were observed. After 4 h the adrenals to pancreas uptake ratio for HYNIC-TOC was higher than that of HYNIC-TATE. Although both compounds had high kidney and low liver excretion, for HYNIC-TATE, it was lower. The results suggest these two new peptide based freeze-dried kits might be of great promise for clinical application in imaging of somatostatin receptor-positive tumors.

Gingivitis is associated with 60-75% of all pregnancies and elevated levels of 17β-estradiol and progesterone is known to increase gingival inflammation and the proinflammatory prostaglandins in the human gingiva. Since cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for the production of prostaglandins at the sites of inflammation, it is plausible to hypothesize that 17β- estradiol and progesterone could contribute to gingival inflammation by upregulation of COX-2 expression and subsequent prostaglandin formation. To examine this hypothesis, primary cultures of human gingival fibroblasts (HGFs) from either sex were established. The cells were treated with different concentrations (10-5, 10-7, and 10-9 M) of 17β-estradiol and progesterone, and expression of COX-2 protein was detected immunocytochemically. The growth potential and proliferation of these cells were studied using trypan blue exclusion method and MTT assay. The results show that both 17β-estradiol and progesterone upregulate COX-2 expression in the HGFs significantly. In addition, progesterone is more effective than 17β-estradiol to induce COX-2 expression at 10-5M but not at lower concentration (10-9M). Furthermore, cells prepared from either sex do not show any difference in COX-2 expression following hormone treatment and neither hormones show any changes in proliferation of these cells. In conclusion, the results of this investigation clearly illustrate significant regulatory effects of 17β-estradiol and progesterone on COX-2 expression in the cultured HGFs. Thus, one possible pathogenetic mechanism of the female sex hormone-associated gingivitis in vivo may be the synthesis of proinflammatory prostaglandins via upregulation of COX-2 expression by gingiva in response to elevated levels of circulating estrogens and progesterone.

Nitric oxide (NO) is a free radical molecule, produced by most cells and tissues in the body. The effect of NO on cells is concentration dependent. Low concentration of NO is essential in biology and physiology of most of cells, but high amounts of NO is toxic and has detrimental effects on cells. The role of NO in biology of male and female genital systems is under investigation. In the present study, the nitric oxide concentration was measured in the seminal plasma of both fertile and infertile males and compared with spermatogram parameters. For this purpose, semen samples were collected from 45 patients and 70 healthy donors. After analysis of samples, the stable metabolites of nitric oxide (nitrite and nitrate) were measured by Griess assay. The results indicated that the nitric oxide concentration in the seminal plasma of infertile males was significantly higher than controls. There was a significant negative correlation between the nitric oxide concentration and sperm motility and viability in infertile males. In conclusion, this study demonstrated that the level of nitric oxide in seminal plasma of infertile men was higher than that of fertile men. The increasing level of nitric oxide concentration in seminal plasma leads to the decrease in sperm motility and viability and affects fertility.

Vitis vinifera (grape) leaf has been used traditionally to treat diarrhea and its extract induces relaxation in rat aorta and uterus. The aim of present study was to investigate the effect of grape leaf hydroalcoholic extract (GLHE) on rat colon contractions induced by some spasmogens. A piece of distal colon from male adult Wistar rats were dissected and mounted in an organ bath containing Tyrode solution and colon contractions recorded by an isotonic transducer under 1g resting tension. The GLHE (0.5- 4 mg/ml) reduced the contractions induced by KCl (60 mM), BaCl2 (4 mM), acetylcholine (1 μM) dose-dependently (P<0.001). The spasmolytic effect of GLHE on ACh-induced contraction was unaffected by propranolol (1 μM), phentolamine (1 μM), L-NAME (300 μM), and naloxone (1μM). In Ca2+-free but rich in KCl (120 mM) Tyrode solution, cumulative concentrations of CaCl2 induced colon contractions which, were inhibited by the extract. Glibenclamide (3 μM) had no effect on the extract spasmolytic activity, but tetraethylammonium (5 mM) contracted the pre-relaxed colon induced by the extract. Results suggest that the grape leaf hydroalcoholic extract spasmolytic effect is due to the blockade of the voltage dependent calcium channels and activation of Ca2+-operated potassium channels

Several therapeutic effects including antimicrobial, antidiarrhea, hepatoprotection and cardiotonic for Berberis vulgaris have been described. In the present study, the effects of hydro-ethanolic extract of Berberis vulgaris on the rate and contractility of isolated heart were examined. The heart mounted on a modified Langendorff apparatus and circulation was perfused through aorta. Heart rate and contractility were determined in the presence of four concentrations of hydro-ethanolic extract (0.5, 1.0, 2.0 and 5.0 mg/100ml) and diltiazem, a calcium channel blocker (0.1, 1,10 and 100 µM) in comparison with baseline values in two different groups of experiments as follows: 1) Perfused heart with normal Krebs solution (group1 experiments, n=10). 2) Perfused heart with calcium free Krebs solution (group 2 experiments, n=9). In group 1 only 3 highest concentrations of diltiazem showed significant reduction in heart rate (p<0.05 to P<0.001). However, 3 highest concentrations of diltiazem showed significant decrease and the last 2 concentrations of hydro-ethanolic extract increased heart contractility significantly (p<0.01 to P<0.001). In group 2 only the last concentration of diltiazem showed significant reduction in heart rate and contractility (p<0.05). The relationship between concentrations of hydro-ethanolic extract and heart rate in both group were negative (p<0.01 to p<0.001). However, there was positive correlation between concentrations of hydro-ethanolic extract and heart contractility. These results showed that of hydro-ethanolic extract of Berberis vulgaris has strong effect on heart contractility. The results of the present study may also indicate an activatoion of the calcium channel of isolated heart by the extract.

From the hexane extract of the aerial parts of Ferulago Bernardii (Apiaceae) four coumarins, namely prantschimgin 1, oxypeucedanin 2, psoralen 3 and umbelliferone 4; β-sitosterol 5; and nonacosane 6 were isolated by Column Chromatography (CC), Preparative Thin Layer Chromatography (PTLC) and crystallization. The structures were elucidated by melting point, UV, IR, MS, 1H and 13C-NMR spectra. The presence of compounds 1, 2, 3 and 5 in some others Ferulago species could be used as chemotaxonomic marker in genus Ferulago. This is the first report on phytochemical analysis of Ferulago Bernardii Tomk. & M. Pimen.

Pre-existing malnutrition has been reported to affect a high percentage of cancer patients. Various methods are being used to assess nutritional status in hospitalized patients. The aim of this study was to apply two different nutritional assessment techniques to determine the prevalence of malnutrition in GI cancer patients and to assess their nutritional status, at admission and seven days after surgery. For this purpose, the nutritional status of fifty one patients who underwent major intraabdominal surgery was assessed. The Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), anthropometric measurements, serum albumin, prealbumin, lymphocyte count and hematocrit were used to assess nutritional status of the patients. At the time of admission, based on the SGA and NRI, 70.6% and 74.5% of the patients were malnourished respectively. Both anthropometric and laboratory data, including weight, body mass index, mid arm circumference, triceps skin fold, mid arm muscle circumference, albumin, prealbumin, hematocrit and lymphocyte decreased significantly seven days after surgery (p<0.01). The malnutrition rates increased significantly to 98% with both the SGA and NRI, seven days after surgery (p<0.01). From the findings of this study it is concluded that there was a high prevalence of malnutrition in GI cancer patients and in almost all patients, nutritional status deteriorated seven days after surgery. Both methods proved useful for detection of the prevalence and development of malnutrition. Based on these results it is suggested that nutritional care after surgery should be improved by providing enough calories via enteral and/or parenteral route.