Expression of alternatively spliced variants of Na-Ca-exchanger-1 in experimental colitis: role in reduced colonic contractility.

Inflammation-induced colonic motility dysfunction is associated with a disturbance in Ca(2+) ion transporting mechanisms. The main objective of this study was to identify the types of Na-Ca-exchanger-1 (NCX-1) variants expressed in the rat colon, and how this was affected by colitis. In addition, the effect of colitis on the possible involvement of NCX-1 in the reduced carbachol-induced contraction of the rat colon was examined. Colitis was induced in male Sprague-Dawley rats by intra-rectal instillation of trinitrobenzenesulphonic acid (TNBS). Animals were killed on day 5. Colitis was characterized by estimating myeloperoxidase (MPO) activity, body weight, and histological scores. NCX-1 mRNA and protein variants were confirmed by RT-PCR coupled nucleotide sequencing and by Western blot analysis, respectively. Contractility of the colon segments was studied using standard procedure. There was a significant reduction in body weight of TNBS-treated rats. A significant increase in MPO activity and infiltration of inflammatory cells were observed in the inflamed rat colon. RT-PCR coupled nucleotide sequencing identified NCX-1.3 mRNA variant containing exons B and D. Western blot analysis confirmed 70 and 120 kDa molecular mass NCX-1 protein variants in rat colon. There was no significant difference (p > 0.05) in the level of NCX-1 protein variants in inflamed colon as compared to non-colitis controls. Functional experiments demonstrated that NCX in reverse mode played a role in carbachol-induced contraction of colon, and this was not affected by colitis. These findings demonstrated expression of a NCX-1.3 mRNA splice variant, and 70 and 118 kDa protein variants. Inhibition of the reverse mode of NCX-1 was not different in reduced carbachol-induced contraction between the groups. These findings are interpreted to suggest that NCX-1, though expressed did not play a role in reduced contractility in experimental colitis.

Type 2 diabetes in the First Nations population: a case example of clinical practice guidelines.

CONTEXT: Type 2 diabetes (T2D) is a major public health concern and has reached epidemic proportions in the Canadian First Nation population. Reasons for this epidemic are the consequences of low socioeconomic status, and challenges to screening, primary prevention, management and access to care. ISSUE: This article presents the authors' opinions of the healthcare needs specific to the First Nation population in Canada with respect to management of T2D. LESSONS LEARNED: The authors argue that the current Canadian Diabetes Association Clinical Practice Guidelines are insufficient to provide a basis for health care and funding policies related to T2D management in the First Nation population. The authors present their own recommendations in relation to funding policies and the appropriateness of services for the First Nation population.

Efficacy of diphtheria and tetanus vaccination in Gaza, Palestine.

This study evaluated the effectiveness and usefulness of vaccination against diphtheria and tetanus in different age groups in Gaza, Palestine. Blood samples were collected from 180 children aged <12 years, 90 males and 90 females. Using ELISA methods, the efficacy of vaccination was estimated at 87.8% for diphtheria and 98.3% for tetanus. Mean serum titres varied significantly by age group: for diphtheria 0.24 IU/mL at age 2-4 years, 0.63 IU/mL at 7-8 years and 0.46 IU/mL at 11-12 years, and for tetanus 1.01 IU/mL, 2.63 IU/mL and 1.20 IU/mL respectively. The relatively low antibody titres, especially for diphtheria, suggest the need for a booster dose.

Efficacy of diphtheria and tetanus vaccination in Gaza, Palestine

This study evaluated the effectiveness and usefulness of vaccination against diphtheria and tetanus in different age groups in Gaza, Palestine. Blood samples were collected from 180 children aged < 12 years, 90 males and 90 females. Using ELISA methods, the efficacy of vaccination was estimated at 87.8% for diphtheria and 98.3% for tetanus. Mean serum titres varied significantly by age group: for diphtheria 0.24 IU/mL at age 2-4 years, 0.63 IU/mL at 7-8 years and 0.46 IU/mL at 11-12 years, and for tetanus 1.01 IU/mL, 2.63 IU/mL and 1.20 IU/mL respectively. The relatively low antibody titres, especially for diphtheria, suggest the need for a booster dose

Alterations of neutrophil functions in foundry and pottery workers.

To assess the immune competence of workers occupationally exposed to mainly silica, neutrophil functions such as the chemotactic and oxidative burst activity in foundry and pottery workers were evaluated. The chemotactic activity was examined in 22 foundry and 10 pottery workers and oxidative burst activity of neutrophils were determined in 22 foundry and 6 pottery workers. Healthy subjects of comparable age, sex, and smoking habits and with no history of silica exposure were used as the control groups. Chemotaxis was carried out in Boyden chambers using Zymosan activated serum as chemotactic stimulus. Oxidative burst activity was measured using nitroblue tetrazolium (NBT) dye reduction test. Both neutrophil functions were significantly reduced in silica-exposed foundry and pottery workers (p < 0.001) compared to controls suggesting that human chronic exposure mainly to silica and other chemicals originated from foundry and pottery settings may diminish neutrophil functions in humans.

Intestinal parasites in relation to haemoglobin level and nutritional status of school children in Gaza.

The prevalence of intestinal parasites and their relations to anaemia and nutritional status among school children aged 6-11 years in Gaza was studied. The target area is overcrowded with improper sewage disposal system and low socioeconomic levels. Anaemia was assessed by haemoglobin level (Hb) and nutritional status by anthropometric measurements including weight for age (WA), weight for height (WH) and height for age (HA). Intestinal parasites were found to be prevalent in Gaza. The overall prevalence was 24.5%. Giardia lamblia (62.2%) was the most common parasite detected particularly in age group 6-7 years, followed by Ascaris Iumbricoides (20.0%), then Entamoeba histolytica (18.0%). Parasitosis was generally declining with older age groups for both sexes. In general, the prevalence of anaemia was more common in the younger children. Malnutrition was found to be prevalent among children. Infected children of age group 8-9 years showed higher incidence of low WA than non infected ones. The prevalence of stunting and wasting among infected children of the youngest group was greater than that observed for controls. Regarding sex, no specific trend that relates the prevalence of anaemia with sex. Malnutrition was more prevalent among females than males.

Prevalence of intestinal parasites among school children in Gaza City, Gaza Strip.

A total of 489 stool specimens were collected from school children aged 6-11 years. The target area is overcrowded, with improper sewage disposal system and low socioeconomic standards. A questionnaire was designed to include relevant informations. Each stool specimen was processed by the direct smear microscopy, zinc sulphate flotation technique and formol-ether sedimentation technique. The present study revealed an overall prevalence at 27.6%. Six parasites were detected. Giardia lamblia (62.2%) was the most frequent species found, followed by Ascaris lumbricoides (20.1%) then, Entamoeba histolytica (13.3%). The prevalence of these parasites was found to be related to age, socioeconomic and sanitation conditions. Most of the other parasitic infections were of mild intensity. There is an urgent need to correct the present situation by improving the living conditions, providing facilities for the population such as modern housing, proper sewage disposal system, health education and execution of survey programs for parasites to treat the infected persons.

Clinical evaluation of a new A.S. mouth wash 881010 as an antismoking agent: a placebo-controlled double-blind trial.

OBJECTIVE: The objective of this study was to assess the effectiveness of a new antismoking (A.S.) preparation manufactured by the Arab Pharmaceutical Manufacturing (APM) Company as an aid to smoking cessation. SUBJECTS, MATERIAL AND METHODS: The design of this clinical study involved 137 Jordanian healthy male smokers. Seventy-four male smokers were given the A.S. mouth wash (active ingredient 0.5% silver nitrate) and 63 male smokers received the placebo solution in a double-blind fashion. Mouth wash solutions were administered three times daily by gargling for one minute and for a period of two weeks. The daily number of cigarettes smoked by volunteers, nicotine, and cotinine concentrations in saliva, plasma, and urine were considered in this study as markers of smoking cessation. RESULTS: Means +/- SD of the number of cigarettes smoked before treatment (zero time) were 21.45 +/- 8.21, and 22.49 +/- 9.50 cigarettes in A.S. mouth wash- and placebo-treated groups, respectively. As compared to placebo, the A.S. mouth wash resulted in a significant (p < 0.05) reduction in the number of daily cigarettes smoked by volunteers during and after treatment. Means +/- SD of the number of cigarettes smoked by A.S. mouth wash-treated volunteers were 8.68 +/- 7.55, 7.87 +/- 6.80, and 10.14 +/- 8.29 cigarettes, and in placebo-treated individuals were 15.91 +/- 8.21, 15.70 +/- 9.58 and 17.03 +/- 9.06 cigarettes, one week, two weeks after treatment, and four weeks after stopping treatment, respectively. Furthermore, a significant number of volunteers either totally stopped or reduced smoking cigarettes after treatment with the A.S. mouth wash. Concerning nicotine and cotinine levels in biological fluids, a trend of a decrease in their levels was observed but it was found not statistically significant. Apart from reversible brownish to blackish discoloration of teeth and gums, no other side-effects were observed after treatment with the A.S. mouth wash. CONCLUSION: In conclusion, the A.S. mouth wash 881010 is generally safe, easy to administer, and effective as an aid to smoking cessation.

Toxicity of a new antismoking mouthwash 881010 in rats and rabbits.

Male and female rats and rabbits were used in this study to investigate the acute and subchronic toxicity of a new antismoking (A.S.) mouth wash (0.5% silver nitrate as the active ingredient). The LD50 values for i.p. administration in male and female rats were 35.7 and 37.2 mg/kg body weight, respectively. The corresponding values in male and female rabbits were 113 and 128 mg/kg body weight, respectively. The oral LD50 values of the mouthwash in male and female rats were 428 and 433 mg/kg body weight, respectively. The corresponding values in male and female rabbits were 1261 and 1320 mg/kg body weight, respectively. Postmortem and histopathological examination revealed congestion, edema, hemorrhage, and mucosal necrosis with brown pigment deposition in the upper gastrointestinal and respiratory tracts for the orally treated animals and ascitis, peritoneal fat necrosis, and pigment deposition in i.p. administered animals. Subchronic toxicity involved administration of low (1.5 mg/kg), intermediate (15 mg/kg), and high (150 mg/kg) doses of A.S. mouthwash by swabbing the oral cavity daily for 30 consecutive days. Body weight, hematologic observations, and histopathological examination showed no significant differences between control and treated animals, except for dark coloration in teeth and increased platelet counts in treated rats.

Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant.

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaCO3, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone > Ac-Di-Sol > Primojel > low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.

Bioavailability and pharmacokinetic properties of 2 sustained-release formulations of diclofenac sodium, Voltaren vs inflaban: effect of food on inflaban bioavailability.

In this study, in vitro characterization, bioavailability and pharmacokinetics of 2 different sustained-release diclofenac sodium dosage forms were compared, Voltaren (100 mg tablets), manufactured by Ciba-Geigy and Inflaban (100 mg enteric-coated tablets), manufactured by the Arab Pharmaceutical Manufacturing Company. The in vitro results demonstrated a faster rate of dissolution for Inflaban as compared to Voltaren, but both products exhibited a sustained-release pattern. The bioavailability study was conducted on 20 healthy male subjects who received a single oral dose (100 mg) of each product according to a randomized 2-way crossover design. Blood samples were obtained over a 26-hour period, and drug concentrations were determined by an HPLC method. Concentration time profiles revealed a sustained-release pattern for both products. The Tlag for Voltaren was 0.8 +/- 0.2 h, significantly shorter than for Inflaban (1.7 +/- 0.2 h) indicating a faster rate of absorption from the upper gastrointestinal tract. The Cmax obtained with Voltaren was significantly higher than that obtained with Inflaban (1,161 +/- 102 and 799 +/- 83, respectively). With respect to Tmax and AUC0-26h parameters, both products were not found to be statistically different. Tmax for Voltaren and Inflaban was 4.2 +/- 0.5 and 4.5 +/- 0.4 h, respectively, whereas AUC0-26h values for both products were 5,423 +/- 562 and 5,237 +/- 520 ng x h/ml, respectively. It is believed that the observed differences between Voltaren and Inflaban are mainly due to the fact that Inflaban is designed as an enteric-coated tablet form, with a core tablet having different sustained-release behavior. In addition, the effect of food on the bioavailability of Inflaban was evaluated in randomly selected 6 male volunteers. Our results revealed that, following light and heavy meals, the AUC0-30 and Cmax were minimally affected by food whereas a significant increase in Tmax and Tlag as compared to fasting conditions was observed.

Bioequivalence study of two capsule formulations of omeprazole.

Bioequivalency of Omeraz, a test-product of Arab Pharmaceutical Manufacturing Company (Jordan) and Losec, a reference product by Astra (Sweden), was evaluated by a randomised crossover study on 22 healthy male volunteers. Serum concentrations of omeprazole were measured by an HPLC assay. There were no statistically significant differences between the two products in terms of serum profile and pharmacokinetic parameters including AUC, Cmax, Tlag, Tmax, MRT, Ke and T1/2. The AUC ratios (Omeraz/Losec) for 24 hours and for infinity were respectively 1.02 with a 90% C.L. of 0.88-1.16 and 1.00 with a 90% C.L. of 0.88-1.14. The two products may be considered as bioequivalent in terms of the extent of absorption as indicated by the AUC ratios. However, the confidence limits of Cmax fall outside the FDA accepted range.

Analysis and bioequivalency study on two tablet formulations of co-trimoxazole.

This paper describes an analytical procedure for simultaneous quantification of trimethoprim (TMP) and sulphamethoxazole (SMZ) in serum. Serum samples were rendered alkaline with glycine-sodium hydroxide buffer (pH 9.1) and extracted with ethyl acetate. The reconstituted sample was analysed using reversed-phase C-18 column high-performance chromatography. The mobile phase consisted of 75% triethyl ammonium acetate buffer, 20% methanol and 5% acetonitrile. The analytes were monitored at 289 nm and tetroxoprim was used as an internal standard. The maximum values for intra-day coefficients of variation (CV) for TMP-and SMZ were 5.7 and 2.1%, respectively. Interday CV values were 6.4 and 2.2%, respectively. The method was used to compare the bioavailability of two tablet formulations in terms of their pharmacokinetic parameters following oral administration of the tablets to 18 volunteers.

Effects of chlorhexidine gluconate douche on normal vaginal flora.

The effects of a 0.5% aqueous chlorhexidine gluconate (CHG) douche on the normal vaginal flora of twenty healthy nonpregnant volunteers were investigated. The douche was applied in a premeasured 180-ml quantity daily for 7 consecutive days. Specimens for aerobic and anaerobic culture of the vaginal flora were obtained on 3 occasions from each volunteer, once before and twice after CHG use. The culture results were analyzed qualitatively and quantitatively. A blood sample was also collected within 24 h of the last CHG application to determine serum CHG concentration. Lactobacillus spp., Gardnerella vaginalis and Staphylococcus epidermidis were the most prevalent aerobic bacteria at all phases of the study and Bacteroides spp. were the most prevalent anaerobes. The composition of the normal flora was essentially the same 30 days after the last dose as the pretreatment flora. Small amounts of CHG were detected in the serum of all but one subject. No untoward effects on the participants were observed. Candida albicans counts were slightly higher, but prevalence was not significantly increased at the end of the study.

A bioequivalence study of two products of furosemide tablets.

Twenty healthy male volunteers participated in a balanced crossover comparison of diusemide versus lasix. Each treatment was given as a single 40 mg tablet following an overnight fast. Furosemide concentration in plasma were determined up to 8 h after treatment. Urine output and urinary sodium excretion was also measured. At the 5% confidence level, no significant difference was found between the area under the plasma concentration-time curves of the two products. The Cmax, tmax, cumulative urine volume, cumulative sodium and potassium electrolytes were found not significantly different for both products. Quality control data including assay, content uniformity, disintegration and dissolution indicated that both products passed the pharmacopoeial requirements, U.S.P. XXII and B.P. 1988. In conclusion, diusemide 40 mg is bioequivalent to the brand name lasix.

Comparative bioavailability of two tablet formulations of diclofenac sodium in normal subjects.

A comparative bioavailability study and in vitro characterization were conducted on two commercial products of diclofenac sodium (Voltaren "A" and Inflaban "B") in the form of enteric-coated tablets (25 and 50 mg). The two products were found similar in weight variation and content uniformity and both met the British Pharmacopeia requirements of disintegration for enteric-coated tablets. The dissolution in vitro revealed that product B was characterized by a faster rate compared to product A. The bioavailability of single doses, 2 x 50 and 2 x 25 mg, of each product was carried out respectively, on 14 and 6 normal male volunteers, according to a randomized complete block design. Blood samples were obtained over a 12-hour interval and serum concentrations of the drug were determined using an HPLC assay. The two products were found bioequivalent as assessed by AUC. However, the tmax value was found to be significantly smaller for product B compared to product A indicating that product B is apparently absorbed at a faster rate. Further, product B was characterized by higher Cmax values, although these were not statistically different from the corresponding values of product A. These findings are consistent with the in vitro dissolution pattern of the two products, and the differences in the rate of absorption may have therapeutic implications.

Growth inhibition of Candida albicans and other medically important yeasts by vaginal contraceptive products.

The antifungal effects of two commercially available spermicidal gels (Conceptrol, produced by Ortho Pharmaceutical, Raritan, N.J., and Koromex, produced by Schmid Laboratories, Little Falls, N.J.) as well as pure nonoxynol-9 and boric acid (both components of vaginal contraceptive products) were tested against 50 clinical yeast isolates by the agar dilution method. The formulated products exerted comparable dose-dependent inhibitory effects against all yeasts tested. A 3-fold dilution of the formulated spermicidal products inhibited 90% of the yeast strains tested. To determine if the antifungal effect was due to the spermicidal detergent nonoxynol-9, this compound was tested for antifungal activity but was completely ineffective against Candida albicans in concentrations up to 10%. Boric acid, present in at least one of the products (Koromex), inhibited representative yeasts at a concentration of 0.4%. The relationship of pH and oxygen tension to inhibition by the commercial spermicides was also investigated. The pH values tested ranged from 4 to 7 and had little effect on inhibition; anaerobiosis at pH 7 slightly reduced the inhibitory activity of Conceptrol gel.

Comparison of the pharmacokinetics and pharmacodynamics of two commercial products containing glibenclamide.

This investigation was carried out to evaluate the in vitro dissolution as well as the pharmacokinetic and pharmacodynamic properties of two tablet oral dosage forms of glibenclamide, Daonil (product A) and Glucomid (product B). The two products were found to comply with the compendial requirements for both disintegration and content uniformity. Further, the in vitro dissolution characteristics of the two products are similar. The bioavailability and pharmacodynamic studies were carried out on 16 healthy male adult volunteers who received a single dose of each product in a double-blind crossover design. Blood samples were obtained over a 12-h interval and analyzed for serum glucose by glucose-oxidase method, insulin by radioimmunoassay and glibenclamide by a sensitive HPLC assay. The two products were not found to be significantly different with respect to peak serum concentrations (187.9 +/- 13.3 and 167.6 +/- 9.1 ng.ml-1 for A and B, respectively) or to the corresponding peak times (4.2 +/- 0.2 and 4.1 +/- 0.2 h for A and B, respectively). Furthermore, the two products were not found significantly different in the extent of absorption as indicated by the area under serum concentration-time curve (1,118.0 +/- 86.7 and 986.5 +/- 75.1 ng.h.ml-1 for A and B, respectively). The two products were also found to be pharmacodynamically equivalent. This was reflected by the comparable serum glucose and insulin levels. These levels correlated very well with glibenclamide concentrations after the administration of each product. These findings indicate that the two products are bioequivalent in terms of bioavailability and pharmacodynamic effects in normal healthy males.

The influence of binder concentration on the bond formation of pharmaceutical granules.

The formation of particle mucilage bonds with dicalcium phosphate dihydrate and starch mucilage binder reduces the B.E.T. nitrogen adsorption surface are from 196 to 0.96 m2 g-1. The maximum reduction (40%) of granule surface area at a binder concentration of 10% w/w corresponded to similar optima in friability, compressability and median granule size. Surface and pore-void structural analysis by mercury intrusion could not discriminate between pore-void sizes in the range 0.5-100 nm. Nitrogen adsorption measurements showed, however, that the microporous surface area decreased from 0.3 to 0.18 m2 g-1 as binder surface coverage increased over the concentration range 2 to 20% w/w starch mucilage.