Therapeutic appraisal of ephedrine against rheumatoid arthritis: A new indication.

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.

Diabetes-related Knowledge, Medication Adherence, and Health-related Quality of Life: A Correlation Analysis.

CONTEXT: Even though positive treatment outcomes for type 2 diabetes mellitus (T2DM) are linked to disease knowledge and adherence to medications, inadequate knowledge, poor adherence, and resistance to lifestyle modifications are still common among patients. This situation has been a continuing dilemma for patients and healthcare providers, and these factors negatively affect the health-related quality of life (HRQoL) of patients. OBJECTIVE: The current study intended to evaluate the correlations between diabetes-related knowledge, medication adherence, and HRQoL among T2DM patients in Pakistan. DESIGN: The study was designed as a questionnaire-based, cross-sectional descriptive analysis, with participants being selected using a prevalence-based sampling method. SETTING: The study was conducted at four different healthcare institutes namely Sandeman Provincial Hospital, Bolan Medical Complex Hospital, Al-Khair Hospital and Sajid Hospital, Quetta city, Pakistan. PARTICIPANTS: Participants were 300 patients with T2DM who were receiving treatment at public and private healthcare institutes in Quetta, Pakistan. OUTCOME MEASURES: In addition to collection of demographics, the Urdu version of Michigan Diabetes Knowledge Test (MDKT-U), the Drug Attitude Inventory (DAI-10), and the EuroQol EQ-5D were used to assess diabetes-related knowledge, medication adherence and HRQoL, respectively. The relationships among the 3 variables were determined using the Spearmen rho correlation coefficient, and the results were interpreted using Cohen' criteria. SPSS v.20 was used for data analysis, and P < .05 was considered significant for all analysis. RESULTS: The mean diabetes-related knowledge score was 5.83 ± 1.92, indicating participants' lack of knowledge of T2DM. Moderate adherence was reported, with a mean adherence score of 4.94 ± 2.72. Additionally, the mean EQ-5D score was 0.48±0.36, and the mean Visual Analogue Score (VAS) was 54.58 ± 20.28, highlighting poor HRQoL. The Spearman's rho correlation coefficient indicated significant, moderate correlations among all variables (P < .05; r = 0.053-0.231). CONCLUSIONS: The study found limited diabetes-related knowledge, moderate medication adherence, and poor HRQoL among patients with T2DM in Pakistan. Nevertheless, a positive significant correlation revealed that a directly proportional change in one study variable can improve the others.

Comparative hepatoprotective effect of Nigella sativa pre- and post-treatment to rabbits.

Synthetic drugs are associated with adverse side-effects and rapid increase in resistance to most of them inspires to evaluate plants for their therapeutic values. We have been aimed to suggest the medicinal use of Nigella sativa seed aqueous extract to minimize the severity of liver damage via its antioxidant properties and its role in maintenance of cell ion-homeostasis. Annoyances in serum levels of some antioxidants and trace metals in human hepatitis C infected patients were compared with that from acetaminophen-induced hepatotoxic rabbits. Serum analysis of human patients and that of hepatotoxic rabbits have exhibited the same trend of incidence of liver marker enzymes, antioxidant levels, and trace metal concentrations, except for the serum levels of cobalt. Significance of pre-/ or post-treatment of Nigella sativa to acetaminophen induced-hepatotoxic rabbit has also evaluated. NS post-treatment to rabbits has been found effective in normalizing the levels (P<0.001) of serum liver markers; especially the ALP levels, and the antioxidants; with significant effect on the serum catalase levels. However, NS pre-treatment has shown its role (P<0.001) in maintaining the serum nickel and cobalt concentrations. Therefore, we suggest the use of Nigella sativa seeds as pre-/ or post-treatment therapy, and also as supplement to the normal medications of liver infection to normalize the status of cell antioxidants and trace metal concentrations.

Phytochemical analysis and antimicrobial activity of aqueous and methanolic extracts of the flowers of Nelumbium speciosum.

In present investigation aqueous and methanolic extracts of Nelumbium speciosum flowers were screened for phytochemical constituents and antibacterial activity to ascertain their traditional use. Antimicrobial activity of both extracts was tested by Kirby-Bauer disc diffusion method against four Gram positive strains, viz. Staphylococcus aureus (ATCC25923), Streptococcus agalactiae (13813), Bacillus subtilis (ATCC 6633), Staphylococcus epidermidis (ATCC 12228) and four Gram negative bacterial strains Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 27853), Proteus mirabilis (12453) and Klebsiella pneumoniae (10031). Phytochemical analysis showed the presence of tannins, saponins and alkaloids in both extracts while flavonoids and steroids were present only in methanolic extract. Methanolic extract of Nelumbium speciosum flower showed concentration dependent antibacterial activity against all tested strains with maximum zone of inhibition (17.3±0.3mm) against P. aeruginosa. Aqueous extract showed concentration dependent activity against S. aureus, E. coli, B. subtilis and S. epidermidis with maximum antibacterial activity against E. coli (14.3±0.3mm). MIC of methanolic and aqueous extracts was in the range of 0.015-0.251 and 0.0625-0.251 mg/mL, respectively. Results showed that methanolic extract of Nelumbium speciosum exhibits superior antibacterial activity than aqueous extract.

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system.

CONTEXT: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach. OBJECTIVE: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material. MATERIALS AND METHODS: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM. RESULTS: LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets. DISCUSSION: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion. CONCLUSIONS: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

Association Between Diabetes-related Knowledge and Medication Adherence: Results From Cross-sectional Analysis.

Context • Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. To have optimal glycemic control, T2DM patients must have sufficient diabetes-related knowledge and must adhere positively and closely to a prescribed regimen. Medication adherence is a key determinant of therapeutic success in patients with T2DM. However, adherence to medications among T2DM patients varies widely, with estimates ranging from 36%-94%. Objective • The purpose of the study was to assess the level of and the association between diabetes-related knowledge and medication adherence among T2DM patients in Pakistan. Design • The research team conducted a cross-sectional survey. Setting • The study was carried out at the outpatient clinic of a public-sector teaching hospital in Sargodha, Pakistan. Participants • Participants were 392 diabetic patients of the hospital. Outcome Measures • In addition to the collection of data on the demographic and disease-related characteristics of the participants, the Urdu versions of the Morisky Medication Adherence Scale (MMAS-U) and the Michigan Diabetes Knowledge Test (MDKT-U) were used to assess medication adherence and diabetes-related knowledge, respectively. Descriptive statistics were used to determine the demographic and disease characteristics, whereas a Spearman rank correlation was used to measure the association between medication adherence and diabetes-related knowledge. Results • The mean age of the participants was 50.77 ± 9.671 y, with males being the dominant gender (n = 222, 56.6%). The mean duration of diabetes was 5.58 ± 4.09 y. Of the 392 patients, 245 (62.5%) had an average knowledge of diabetes. Furthermore, 282 (71.9%) were categorized as showing poor adherence. A significant but weak positive correlation between diabetes-related knowledge and medication adherence was found for the study (r = 0.036, P < .05). Conclusions • Although diabetes-related knowledge among the patients was average, the adherence to treatment was poor. Because patients' knowledge about diabetes was positively associated with medication adherence, the research team believes that educating patients about the disease and medication management can result in better control of T2DM.

Comparative hypoglycemic activity of different fractions of Thymus serpyllum L. in alloxan induced diabetic rabbits.

The aim of present study was to evaluate and compare the hypoglycemic activity of different solvents extracts of Thymus serpyllum in rabbits. Diabetes was induced with single intravenous injection of alloxan monohydrate (150mg/kg). Glibenclamide and acarbose were used as standard drugs. The crude powder of Thymus serpyllum (500 mg/kg b.w) significantly reduced blood glucose level in both normal and diabetic rabbits. Various extracts of Thymus serpyllum were compared for their hypoglycemic activity in diabetic rabbits. Ether and aqueous extracts significantly reduced the blood glucose level with maximum effect (p<0.001) produced by aqueous extract, which was selected for further study. Aqueous extract significantly inhibited the rise in glucose level in oral glucose tolerance test. The extract showed synergistic effect with different doses of insulin; however serum insulin level of the diabetic rabbits was not significantly increased by the extract. HbA1c level was significantly (p<0.05) reduced whereas hemoglobin level was significantly increased in three months study. Phytochemical screening of the aqueous extract showed the presence of alkaloids, flavonoids, tannins, terpinoids, reducing sugar and cardiac glycosides. It is concluded that the aqueous extract might be used alone or in combination with insulin to manage diabetes and its associated complications.

Bullying, internalized hepatitis (Hepatitis C virus) stigma, and self-esteem: Does spirituality curtail the relationship in the workplace.

The objective of this study was to examine the impact of workplace bullying on self-esteem, including the mediating effect of internalized stigma and the moderating effect of spirituality, among hepatitis C virus patients. Data were collected from 228 employed hepatitis C virus patients who had been admitted to Gastroenterology and Hepatology wards in Pakistani hospitals. We found support for the hypothesis that workplace bullying is associated with low self-esteem via internalized stigma. In addition, spirituality moderated the association such that participants with greater spirituality were buffered from the impact of stigma on self-esteem.

RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

Cardiotonic and vasoconstriction effects of aqueous methanolic extract of Paspalidium flavidum L.

The cardiovascular activity of aqueous methanolic extract of Paspalidium flavidum L. was evaluated on isolated rabbit heart and aorta. Heart rates, force of contraction and perfusion pressure were assessed in the presence of different concentrations of extract and adrenaline by using Langendorff's technique. Moreover, the vasoconstriction effects were studied in rabbit aorta using isolated organ bath. The results indicated that the extract (1ng-100 µ g/ml) exhibited a significant increase in heart rate, contractility and perfusion pressure of isolated rabbit's heart; with a maximum effect at 1ng/ml, which was comparable to adrenaline (1 µ g/ml). Similarly, adrenaline at doses from 1-10 µ g/ml produced a significant dose dependant increase in all the cardiac parameters. The cardiotonic effects of the extract were significantly blocked by propranolol (10(-5)M) while an increase in perfusion pressure was completely antagonized by verapamil (10(-6)M). Activity of cardiac marker enzymes was also significantly raised in the perfusate of isolated heart pretreated with the extract. In rabbit aorta, the extract exhibited a dose dependent vasoconstriction effect however it did not increase the tone of aorta when pre-treated with verapamil (10(-6)M). It is conceivable therefore; that the cardiotonic and vasoconstriction effects of the extract might be due to its agonistic actions on ß-receptors and Ca(+2) channels.

Hypoglycaemic effects of methanolic extract of Canscora decussata (Schult) whole-plant in normal and alloxan-induced diabetic rabbits.

In present study hypoglycaemic effects of the crude powdered C. decussata and its methanolic extract (ME) in alloxan diabetic rabbits were evaluated. The hypoglycaemic effect was measured by blood glucose, insulin level, HbA1c and his to pathology of pancreas. Glucose lowering effect of the ME was studied in diabetic rabbits. The effects of extract on blood glucose, body weight, food in take, fluid intake, OGTT were also evaluated. The results showed that 0.5,1 and 2g/kg of the powder significantly decreased blood glucose levels in normal rabbits and diabetic rabbits at the intervals checked. Oral intake of pioglitazone also reduced the levels in these rabbits. Synergistic hypoglycaemic effect of 600mg/kg of ME with different doses of insulin (2 & 3unit/kg, s/c) further reduced blood glucose levels of treated alloxan-diabetic rabbits. The oral glucose tolerance test revealed lowered area under curve values in ME treated rabbits. Treatment with ME (400 and 600 mg/kg) for 30 days showed highly significant decrease in blood glucose level by augmenting insulin secretion, HbA1cand significant increase in body weight, serum insulin levels in treated diabetic rabbits. Histopathology study showed regeneration of ß-cells. These studies have, therefore, supported the traditional use of this herb in diabetic patients.

Acute toxicity studies of a novel excipient arabinoxylan isolated from Ispaghula (Plantago ovata) husk.

PURPOSE: The arabinoxylan from Ispaghula (Plantago ovata) husk has been proven scientifically as potential excipient. However, toxicity study of the arabinoxylan is still lacking. The present study was done to investigate the acute toxicity of arabinoxylan in two animal species. METHODS: The mice were exposed to (1 g/kg, 5 g/kg, 10 g/kg) and rabbits (2.5 g/kg, 5 g/kg) of arabinoxylan orally and observed for a period of 14 days. On day 15 hematology, serum biochemistry and necropsy was performed in mice relative organ weight calculated and histological examination was carried out. Primary dermal and eye irritation tests were carried out. Cardiac effects of isolated arabinoxylan were studied on frog heart. RESULTS: The acute administration of the arabinoxylan did not produce mortality or significant changes in, water and food consumption however body weights of mice and rabbits decreased initially with a gradual increase till day 14. Internal organs relative weights were found to be normal. Hematological biochemical and histopathological examination did not show any significant (p < 0.05) change. Primary dermal and eye irritation was not observed in treated rabbits. No change in heart rate and vascular contraction was observed in frog heart. CONCLUSION: This study has shown that acute administration of arabinoxylan may be safe.

Possible mechanism of cardiac depressant activity of Berberis orthobotrys roots in isolated rabbit heart.

Berberis orhob, otrvs Bien. ex Aitch. (B.o.) has been reported to have antihypertensive effect in different experimental models. The aim of present study was to evaluate the possible antihypertensive mechanism. Aqueous methanolic extract of B.o. roots and its various fractions namely (ethyl acetate, n-butanol or aqueous) in different concentrations (10 ng/mL, 100 ng/mL, I pg/mL, 10 pg/mL, 100 pg/mL ) were evaluated in isolated perfused rabbit heart to assess their effect on force of contraction, HR and perfusion pressure. The crude extract of B.o. and its fractions exhibited a significant decrease in heart rate, contractility and perfusion pressure of isolated rabbit heart, however, butanolic fraction produced more prominent effect and was selected for further study. The effects of butanol fraction were not blocked by atropine (10' M) in isolated perfused heart. However, butanol fraction significantly blocked the effects of adrenaline (10' M). It is therefore conceivable that cardiac depressant activity of B.o. butanol fraction might be due to the presence of certain 3-blocking agents which might be responsible for antihypertensive effect However, further experiments are required to isolate the active compound(s) and elucidate exact mechanism of action.

Cardiotonic activity of methanolic extract of Saussurea lappa Linn roots.

The cardiac activity of Saussurea lappa roots was evaluated in isolated perfused rabbit heart by the Langendorff's technique. Heart rate, contractility and coronary flow were determined in the presence of different concentrations of methanolic extract of Saussurea lappa, digoxin and diltiazem. The extract exhibited significant (p<0.01) positive inotropic effect at the first three doses (0.5/µg, 2.5/µg and 5.0/µg) while a significant negative chronotropic effect and coronary flow rates were observed at all the doses tested. These effects were comparable to the effects of digoxin and diltiazem. The increase in force of contraction with decrease in heart rate and coronary flow rates were also observed to be dose dependent as increase in the dose of test extract further enhanced the effects except contractility that started decreasing at higher doses. It is conceivable therefore, that Saussurea lappa roots contain certain pharmacologically active compounds that could be involved in the cardiotonic activity of the extract.