Biomedical subjects

C L Kaul

Publications and source records attributed to C L Kaul.

At least 19 recordsLinked to original sources

PubMed2005

AT1 receptors and L-type calcium channels: functional coupling in supersensitivity to angiotensin II in diabetic rats.

OBJECTIVE: The study was designed to investigate the role of calcium channels in enhanced angiotensin II (Ang II)-induced contraction in thoracic aortic rings from diabetic rats. METHODS: Ang II-induced isometric tension was studied in thoracic aortic rings isolated from control or streptozotocin-induced (8 weeks) diabetic rats. Saturation binding studies at AT1 receptors and L-type calcium channels were performed using [3H] Ang II and [3H] PN200110, respectively. Ang II-induced calcium influx was studied in fura-2-loaded single vascular smooth muscle cells isolated from thoracic aorta of control and diabetic rats. RESULTS: Ang II did not induce contraction in calcium-free Krebs. In the presence of extracellular calcium, increased Emax (mg/mm2) and pD2 to Ang II was observed in aortic rings from diabetic (795.54+/-38.19; 8.27+/-0.12) compared to control (230.09+/-25.45; 7.68+/-0.22) rats, respectively. Nimodipine but not verapamil or diltiazem dose-dependently blocked the Ang II-induced contractions in a noncompetitive manner and its -log IC50 was significantly lower in aortic rings from diabetic (8.81+/-0.10) compared to control (9.34+/-0.11) rats. The Ang II-induced increase in intracellular calcium levels was significantly enhanced (2.5-fold) in vascular smooth muscle cells from diabetic rats. AT1 receptor saturation binding with [3H] Ang II revealed a significantly higher affinity (nM) and Bmax (pmol/mg protein) in aortic vascular membrane preparation from diabetic (0.31+/-0.04; 64.18+/-2.4) compared to control (0.52+/-0.02; 47.81+/-2.8) rats, respectively, while L-type calcium channel saturation binding with [3H] PN200110 showed a higher affinity (nM) with no change in the Bmax (fmol/mg protein) in diabetic (0.74+/-0.08; 4.52+/-0.40) compared to control (1.49+/-0.32; 5.43+/-0.60) aortic membranes, respectively. CONCLUSIONS: Our results suggest that Ang II-induced contraction is dependent on extracellular calcium, and enhanced functional coupling of AT1 receptors and DHP-sensitive L-type calcium channels results in supersensitivity to Ang II in thoracic aorta isolated from diabetic rats.

Angiotensin II↗

PubMed2005

Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine, a new hope.

Alzheimer's disease is the fourth largest cause of death for people over 65 years of age. Dementia of Alzheimer's type is the commonest form of dementia, the other two forms being vascular dementia and mixed dementia. At present, the therapy of Alzheimer's disease is aimed at improving both, cognitive and behavioural symptoms and thereby, quality of life for the patients. Since the discovery of Alzheimer's disease by Alois Alzheimer, many pathological mechanisms have been proposed which led to the testing of various new treatments. Until recently the available drugs for the treatment of Alzheimer's disease are cholinesterase inhibitors, which have limited success because these drugs improve cognitive functions only in mild dementia and cannot stop the process of neurodegeneration. Moreover, drugs of this category show gastrointestinal side effects. As the cells of central and peripheral nervous system cannot regenerate, newer strategies are aimed at preserving the surviving neurons by preventing their degeneration. NMDA-receptor-mediated glutamate excitotoxicity plays a major role in Abeta-induced neuronal death. Hence, it was thought that NMDA receptors could be a promising target for preventing the progression of Alzheimer's disease. All the compounds synthesized initially in this category showed toxicity mainly because of their high affinity for NMDA receptors. Memantine (1-amino adamantane derivative), NMDA-receptor antagonist was reported to be effective therapeutically in Alzheimer's disease. It was available in Germany as well as European Union and has been approved for moderate to severe dementia in United States of America recently. It is an uncompetitive, moderate affinity antagonist of NMDA receptors that inhibits the pathological functions of NMDA receptors while physiological processes in learning and memory are unaffected. Memantine is also reported to have beneficial effects in other CNS disorders viz., Parkinson's disease (PD), stroke, epilepsy, CNS trauma, amyotrophic lateral sclerosis (ALS), drug dependence and chronic pain. Mechanisms of neuroprotection, preclinical and clinical evidence for effectiveness of memantine have been provided. Pharmacology and pharmacokinetics of memantine and other NMDA-receptor antagonists in comparison with currently approved drugs for dementia treatment have been discussed. The focus is on 'glutamate excitotoxicity' and glutamate receptors as drug target. Various other novel strategies for the treatment of dementia of neurodegenerative disorders have also been discussed.

Alzheimer Disease↗

PubMed2005

Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening.

The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.

Animals↗

PubMed2005

Determination of rifampicin bioequivalence in a three-drug FDC by WHO and indian protocols: effect of sampling schedule and size.

SETTING: To promote the quality assurance of fixed-dose combination (FDC) formulations, the World Health Organization (WHO) has prepared a convenient simplified protocol for the determination of rifampicin (RMP) bioequivalence. During the development of this protocol, it was proved that sampling time up to 8 h can determine the rate and extent of RMP absorption. However, this protocol utilises 20 volunteers in contrast to other local regulatory requirements of a minimum of 12 volunteers. The different sample sizes utilised in these protocols may affect the sensitivity of the bioequivalence outcome. OBJECTIVE: To determine the effect of sampling size and schedule on RMP bioequivalence when two different protocols are used. DESIGN: A bioequivalence trial was conducted with a study design of 20 volunteers and 24 h sampling time, which fulfils the requirements of both the WHO and Indian regulatory protocols. Pharmacokinetic and statistical analysis was done by stepwise reduction in sample size and schedule. RESULT: Bioequivalence limits of RMP were unaffected by a reduced sample size of 12 volunteers and 8 h sampling time. CONCLUSION: Minimising sample size after validation for borderline and poor quality FDC formulations can further reduce the cost of conducting bioequivalence trials.

Absorption↗

PubMed2005

A study on alpha-adrenoceptor mediated contractile responses of high fat diet fed rat thoracic aorta.

Feeding rats with high fat diet (HFD) leads to the various conditions of syndrome-X. These are associated with hypertension through a variety of mechanisms. Vascular abnormalities probably contribute to the etiology of many diabetic complications. There is an increase in maximal responses to various agonists with blood vessels of streptozotocin induced diabetic animals. The purpose of this study was to evaluate the development in HFD fed rats for altered biochemical parameters, to assess the vascular responses to phenylephrine (PE), to estimate the KA values and to observe the receptor occupancy. Body weights, plasma triglycerides, cholesterol, and glucose levels were measured every week in male Sprague-Dawley rats. Glucose tolerance test was performed after 4 weeks of feeding. At the end of the fourth week of feeding, concentration-response curves of PE were recorded. Altered KA values of PE (NPD fed rats 2.0 +/- 0.4 microM and HFD fed rats 0.3 +/- 0.1 microM) and receptor occupancy response (NPD fed rats 92.1 +/- 1.7% and HFD fed rats 77.5 +/- 5.6%) strongly suggest that hypertension in HFD fed rats is associated with altered alpha-adrenoceptor function.

Adipose Tissue↗

PubMed2005

Plasma pooling: utility in expediting bioequivalence assessment of rifampicin-containing fixed-dose combinations.

To improve the rapidity of the registration process of rifampicin (RMP) containing fixed-dose combination (FDC) formulations, a plasma pooling methodology was used to increase the throughput of bioanalysis of plasma samples from bioequivalence trials of FDCs. Plasma samples of a biostudy were analysed for RMP using traditional analysis methods as well as a plasma pooling method (volunteer and time pooling). Both methods produced similar results, with less than 15% variability in both volunteer and time pooling. The plasma pooling method for bioanalysis was validated. Further studies are required to identify and reduce the percentage variability.

Antibiotics, Antitubercular↗

PubMed2005

Establishment of a reference formulation for bioequivalence assessment of rifampicin-containing FDCs: an essential step towards improving tuberculosis treatment.

SETTING: Selection of a reference product for bioequivalence studies of rifampicin (RMP) in prequalifying fixed-dose combinations (FDC) for worldwide distribution through the WHO is critical. OBJECTIVE: To investigate the feasibility of establishing FDC formulations as reference products for bioequivalence studies of RMP in prequalification programmes. DESIGN: A biostudy was conducted as an open, two-period randomised cross-over trial. Two three-drug FDCs containing RMP, isoniazid and ethambutol hydrochloride were administered to a group of 22 volunteers with a wash-out period of 1 week. Plasma samples were collected and analysed for the concentration of RMP and desacetyl-RMP, a major active metabolite of RMP, up to 24 h. Pharmacokinetic parameters of RMP were calculated: Cmax, AUC0-24, Tmax, kel and absorption efficiencies. RESULTS: No significant difference was observed between the administered formulations with respect to the major pharmacokinetic parameters Cmax, Tmax and AUC0-24 when evaluated by parametric (two-way ANOVA) and non-parametric (Hauschke's analysis) statistical analysis. The concentration of RMP falls within the reported acceptable therapeutic range. CONCLUSION: FDCs can be developed as a reference product for bioequivalence studies.

Antibiotics, Antitubercular↗

PubMed2005

Quality control of anti-tuberculosis FDC formulations in the global market: part II-accelerated stability studies.

OBJECTIVE: To determine the quality and performance of rifampicin (RMP) containing fixed-dose combination (FDC) formulations of anti-tuberculosis drugs sourced from the international market with respect to physical, chemical and dissolution properties after storage at accelerated stability conditions (40 degrees C/75% relative humidity) and to identify appropriate storage specifications. METHODS: Formulations across different companies and combinations were subjected to 6-month accelerated stability testing in packaging conditions recommended by the manufacturer. Various pharmacopeial and nonpharmacopeial tests for tablets were performed for 3- and 6-month samples. RESULTS: All the formulations were found to be stable, where extent of dissolution was within +/- 10% of that of the initial value, and all formulations passed the pharmacopeial limits for assay and content uniformity of 90-110% and +/- 15% of average drug content, respectively. CONCLUSIONS: Good quality RMP-containing FDCs that remain stable after 6-month accelerated stability testing are available in the marketplace.

Antibiotics, Antitubercular↗

PubMed2005

Minimum sample size and sampling time requirements for assessment of rifampicin bioequivalence from FDC formulations.

SETTING: The WHO- and IUATLD-recommended protocol for rifampicin (RMP) bioequivalence utilises 20-22 volunteers and 8 h, whereas the requirement of other regulatory authorities is 12 volunteers with a 24 h sampling schedule. Differing sampling size and time requirements may change the outcome of RMP bioequivalence. OBJECTIVE: To determine the minimal sample size and time required to assess RMP bioequivalence from FDC formulations. DESIGN: Bioequivalence studies were conducted that fulfilled the criteria of the WHO and Indian regulatory protocols. From earlier studies, retrospective pharmacokinetic evaluation, power of the test and bioequivalence limits were also calculated using 8-22 volunteers and sampling points of 8-24 h. Pharmacokinetic and statistical evaluations from three representative studies showing low, moderate and high intra-subject variability are given to determine minimum requirements for RMP bioequivalence. RESULT: It was found that a sampling schedule up to 8 h was sufficient to compare the absorption process of RMP. There was no influence of reduced sample size on bioequivalence estimates of RMP that showed low or moderate variability. However, in a study showing higher variation, a sample size of 14-16 subjects was found to be optimal. CONCLUSION: It is possible to reduce the sample size requirement for determination of RMP bioequivalence using the WHO protocol.

Antibiotics, Antitubercular↗

PubMed2005

Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P < 0.05) change in permeability in the presence of GFJ. Chronic administration of GFJ resulted in a significant decrease in absorptive transport of indinavir, which was even greater than that produced by rifampicin pretreatment. No change in permeability of propranolol, a passive permeability marker, was observed. Further, the decrease in absorptive transport of INDI was reversed by the P-gp inhibitor verapamil. In conclusion, GFJ extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague-Dawley rats: reversal by adenosine.

Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.

Adenosine↗

PubMed2004

High glucose concentration augments angiotensin II mediated contraction via AT1 receptors in rat thoracic aorta.

Elevated glucose concentration is implicated to play major role in development of diabetic associated vascular complications. It was previously reported that angiotensin II (Ang II) induced contractile response is enhanced in thoracic aorta of diabetic rats. In the present study, the effect of high glucose (HG, 25 mM) exposure for 2h on Ang II cumulative concentration response curves recorded isometrically was studied in thoracic aortic rings isolated from male Sprague-Dawley rats pretreated with streptozotocin (STZ, 65 mg kg(-1) i.p.) or vehicle at 8 weeks prior to the study. Ang II induced contraction via AT1 receptor was significantly enhanced (by 60 +/- 2 %) in HG exposed thoracic aortic rings isolated from vehicle treated but not STZ treated rats. However, there was no change in the pD2 of Ang II while potassium chloride (KCl) induced contraction was unaltered. Ang II induced contractile response was blocked by valsartan (100 microM, selective AT1 receptor antagonist) but not PD 123,319 (100 microM, selective and potent AT2 receptor antagonist). Exposure of aortic rings from control rats to 25 mM mannitol or sucrose for 2 h did not have any effect on the Ang II induced contraction. Tempol (100 microM, a cell permeable superoxide dismutase mimetic) partially reduced the augmented Ang II response in HG exposed aortic rings, while it did not affect the Ang II responses in normal glucose (NG 5.5 mM) exposed aortic rings isolated from control rats. [3H] Ang II binding at AT1 receptors was unaltered in vascular smooth muscle membranes prepared from thoracic aorta exposed to HG for 2 h compared to NG exposed aortic rings. From our results, we conclude that high glucose concentration augments Ang II mediated contraction via AT1 receptors and reactive oxygen species partly contribute to this augmented contraction.

Angiotensin II↗

PubMed2004

Reversal of glucose intolerance by by pioglitazone in high fat diet-fed rats.

The present study was undertaken to determine the effect of pioglitazone (3, 10 and 30 mg/kg p.o.), an insulin sensitizer, on glucose intolerance in high fat diet- (HFD) fed rats (a nongenetic model of insulin resistance). In addition, the effect of pioglitazone (3, 10 and 30 mg/kg p.o.) on diet-induced changes in body weight, plasma glucose, insulin, triglyceride and total cholesterol levels were also determined. The feeding of HFD for 4 weeks produced a significant increase in body weight, total fat pad weight, basal/fasting plasma glucose, insulin, basal triglyceride (TG) and total cholesterol (TC) levels in male rats. Furthermore, the rats fed HFD exhibited fasting hyperglycemia and hyperinsulinemia as well as enhanced glycemic response to exogenously administered glucose (2 g/kg p.o.) during an oral glucose tolerance test (OGTT) at the end of 4 weeks of dietary manipulation, indicating that the rats had developed insulin resistance and glucose intolerance. Treatment with pioglitazone (10 and 30 mg/kg p.o.) once daily for 2 weeks significantly diminished the elevated basal plasma insulin and TG levels in HFD-fed rats. In addition, a statistically significant reduction in TC level was observed only with the high dose of pioglitazone (30 mg/kg p.o.). However, pioglitazone had no significant effect on body weight, total fat pad weight and basal plasma glucose level. Pioglitazone (10 and 30 mg/kg p.o.) significantly reduced fasting hyperglycemia and reversed oral glucose intolerance to normal in HFD-fed rats compared with control normal rats. The above findings suggest that pioglitazone has potent insulin-sensitizing and lipid-lowering properties in a HFD-fed rat model. In conclusion, the present study demonstrates that the adult male rats on a HFD for 4 weeks exhibited the characteristic features of obesity, insulin resistance and glucose intolerance, namely increased body weight, increased total fat pad weight, mild basal/fasting hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and impaired oral glucose tolerance, that closely resemble the human prediabetic obese insulin-resistant and glucose-intolerant state. Further treatment with pioglitazone once daily for 2 weeks significantly ameliorated changes in basal plasma insulin, TG and TC, and reversed oral glucose intolerance to normal in HFD-fed rats, suggesting its potential in the treatment of insulin resistance and glucose intolerance associated with abnormal lipid metabolism.

Animals↗

PubMed2004

Quality control of anti-tuberculosis fixed-dose combination formulations in the global market: an in vitro study.

OBJECTIVE: To determine the quality, and especially the dissolution properties of rifampicin, of fixed-dose combination (FDC) formulations of anti-tuberculosis agents manufactured by major market holders in the anti-tuberculosis sector and supplied for use in national tuberculosis control programmes. METHODS: Dissolution studies were performed for four formulations supplied by four different manufacturers in four dissolution media (0.1N and 0.01N HCl, phosphate buffer [PB] and 20% vegetable oil in PB), at four different agitation rates using USP apparatus II. The formulations were subjected to 4-week accelerated stability studies (40 degrees C / 75% RH) and evaluated for physical, chemical and dissolution stability. RESULTS: The formulations tested complied with pharmacopeial quality control (QC) tests. The extent of rifampicin release was independent of dissolution medium; however, a slight decrease in the dissolution rate was observed in two products. More than 75% of drug was released in 45 min at all agitation intensities except 30 rpm, and 20% oil in the medium reflected fed state. Formulations were stable in the packaging conditions recommended by the manufacturer for at least 4 weeks. CONCLUSIONS: The formulations tested passed the QC tests and were found to be stable. A decrease in the rate, although not the extent, of dissolution necessitated multiple point dissolution in gastric and intestinal pH conditions to ensure consistency in in vivo bioavailability.

Antibiotics, Antitubercular↗

PubMed2003

Protective effect of a polyherbal formulation (Immu-21) against cyclophosphamide-induced mutagenicity in mice.

The object was to evaluate the effects of a polyherbal formulation, Immu-21, against cyclophosphamide (CP)-induced chromosomal aberrations (CA) and micronuclei (MN) in mice. CP alone (40 mg/kg, i.p.) produced classical as well as non-classical chromosomal aberrations in mice, and the incidence of CA was significantly more in the CP treated group when compared with that of the control group. Immu-21, which contains extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia, was given at 100 mg/kg, daily, over 7 days, and 30 mg/kg daily over 14 days and inhibited both CP-induced classical and non-classical chromosomal aberrations ( approximately 40%-60% of control). A significant increase in MN was also observed in bone marrow erythrocytes of mice treated with CP, and pretreatment with Immu-21 also significantly reduced these. Cytotoxicity was evaluated by estimating the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The present results indicate that chronic treatment with Immu-21 prevented CP-induced genotoxicity in mice.

Animals↗

PubMed2002

Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Analysis of Variance↗

PubMed2002

Cell proliferation and natural killer cell activity by polyherbal formulation, Immu-21 in mice.

Immunomodulatory activity of an Ayurvedic polyherbal formulation, Immu-21 containing extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia was studied on proliferative response of splenic leukocytes to T cell mitogens, concanavalin (Con)-A and phytohemagglutinin (PHA) and B cell mitogen, lipopolysaccharide (LPS) in vitro by [3H]-thymidine uptake assay in mice. The cytotoxic activity of Immu-21 was tested by measuring the splenic leukocyte natural killer (NK) cell activity against K 562 cells. Intraperitoneal (i.p.) treatment with Immu-21 (30 mg/kg) once a day for 14 and 21 days did not cause change in body weight and spleen weight, where as splenocytes/spleen count was increased. Treatment of Immu-21 (30 mg/kg, i.p.) for 14 days and 1 mg/kg for 21 days significantly increased LPS induced leukocyte proliferation. NK cell activity was significantly increased when mice were pretreated with Immu-21 (10 and 30 mg/kg, i.p.) once a day for 7 days. The results indicate that pretreatment with Immu-21 selectively increased the proliferation of splenic leukocyte to B cell mitogen, LPS and cytotoxic activity against K 562 cells in mice.

Adjuvants, Immunologic↗

PubMed2001

Sympathetic nervous system and experimental diabetes: role of adrenal medullary hormones.

The sympathetic nervous system is of major importance in the regulation of various physiological functions. The present review discusses the mechanisms which control glucose homeostasis and the role of the sympathetic nervous system in experimental diabetes with special emphasis on the role of adrenal medullary hormones, over-activity of the sympathetic nervous system and its relationship to hypertension in the diabetic state and the effect of stress. The chapter also reviews the ability of various drugs and pharmacological agents to produce hyperglycemia in experimental animals and how this information can be used in screening new chemical entities and in differentiating the mode of action of these agents.

Adrenal Medulla↗