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Biomedical subjects

P N Singh

Publications and source records attributed to P N Singh.

At least 19 recordsLinked to original sources

Evaluation of anti-inflammatory activity of Cissampelos pareira root in rats.

In the present study, 50% ethanolic extract of Cissampelos pareira roots (CPE) in acute, subacute and chronic models of inflammation was assessed in rats. Per os (p.o.) administration of CPE (200, 400 mg/kg) exhibited significant anti-inflammatory activity. In acute inflammation as produced by carrageenin 59.55% and 64.04%, by histamine 15.38% and 30.77%, by 5-hydroxytryptamine 17.78% and 31.11% and by prostaglandin E(2)-induced hind paw edema 19.23% and 30.77% protection was observed. While in subacute anti-inflammatory models using formaldehyde-induced hind paw edema (after 1.5 h) 38.36% and 47.95% and in chronic anti-inflammatory model using cotton pellet granuloma 15.02% and 19.19% protection from inflammation was observed. CPE did not show any sign of toxicity and mortality up to a dose level of 1000 mg/kg, p.o. in rats. Both acute as well as chronic administration of CPE (100, 200 and 400 mg/kg, p.o.) did not produce any gastric lesion in rats. These data indicate that CPE possesses significant anti-inflammatory activity without ulcerogenic activity suggesting its potential as an anti-inflammatory agent for use in the treatment of various inflammatory diseases.

Animals↗

Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino rats.

Administration of an aqueous extract of fruits of Withania coagulans (1 g/kg; p.o.) to high fat diet induced hyperlipidemic rats for 7 weeks, significantly reduced elevated serum cholesterol, triglycerides and lipoprotein levels. This drug also showed hypolipidemic activity in triton induced hypercholesterolemia. The histopathological examination of liver tissues of treated hyperlipidemic rats showed comparatively lesser degenerative changes compared with hyperlipidemic controls. The hypolipidemic effect of W. coagulans fruits was found to be comparable to that of an Ayurvedic product containing Commiphora mukkul.

Albinism↗

Hypoglycemic activity of Withania coagulans Dunal in streptozotocin induced diabetic rats.

Administration of aqueous extract of fruits of Withania coagulans Dunal significantly lowered the blood sugar, serum cholesterol, serum LPO, and hepatic LPO levels at the highest concentration of 1g/kg; p.o. in streptozotocin induced diabetic rats. In normal rats as well the blood sugar levels were significantly decreased following treatment with the above drug. Withania coagulans also exhibited free radical scavenging activity in an in vitro system using DPPH.

Animals↗

Simplified [correction of Simlified] calculation of mean QRS vector (mean electrical axis of heart) of electrocardiogram.

In clinical practice assessment of the mean QRS axis (MQRSA) provides information related either with hypertrophy of the ventricles or conduction blocks. The method adopted by clinicians i.e. the inspection of the QRS voltage in six of the limb leads has inherent element of subjectivity of approximately 10degrees. Moreover, in certain condition, when there is ambiguity about differentiation of left axis deviation assessed by inspection method in to either hypertrophy of left ventricles or complete/hemi block of the left bundle branches, accurate measurement of the axis becomes necessary to arrive at the correct diagnosis. Though a formula based on area under R wave and S-wave of the same QRS complex has been derived for accurate measurement of axis, considering its use in the computer software, working with ordinary electrocardiograph the only method for accurate measurement of the QRS axis is plotting method i. e. the net voltages in Lead-I, and III on their respective axes which is not practicable in clinical settings. Although, calculation of MQRSA by area method gives an accurate assessment of MQRSA, some authors prefer measurement of axis by voltage method, as in cases of the right ventricular hypertrophy with a broad S-wave calculation of axis by area method may give erroneous results. Hence, to obtain correct measurement of MQRSA, we have derived a simplified formula based on the net voltage of QRS complexes in Lead-I and Lead-III. The formula derived is as follows, Tan(theta) =(I + 2III) divided by sqrt [3I], where I and III represent net voltage in Lead-I and III, theta = angle subtended with the axis Lead-I. The value of theta can be found by using scientific calculator or the table. In case net voltage of QRS complex in Lead-I being negative, the value of the theta should be subtracted from 180degrees to find the angle of mean QRS vector.

Humans↗

Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn.

The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500 mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3% carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam.

Amnesia↗

Disseminated Penicillium marneffei infection among HIV-infected patients in Manipur state, India.

OBJECTIVE: To further describe the clinical and epidemiological characteristics of Penicillium marneffei infection in human immunodeficiency virus (HIV) infected patients in India. METHODS: In continuation of our earlier report of four autochthonous cases of P. marneffei infection in HIV infected patients from Manipur, a northeastern state of India, we studied additional 46 cases of penicilliosis marneffei from the same area over a period of 19 months (April 1998-October 1999). Clinical, microbiological features, and therapeutic responses were analyzed in 36 of the 46 patients as ten patients were lost to follow-up. RESULTS: Of the 198 HIV positive patients attending the J. N. Medical Hospital, Imphal, Manipur state during the period mentioned, 46 (25%) had P. marneffei disseminated infection. Of the 36 patients analyzed 31 (86%) were intravenous drug abusers, 1 had multiple sex partners, and 3 females acquired HIV infection from their respective spouses. A 9-year-old child acquired HIV infection by vertical transmission. The common clinical symptoms included fever (97%), weight loss (100%), weakness (86%), anemia (86%), and characteristic skin lesions (81%). Presumptive diagnosis was made by microscopic examination of Wright's-stained smears of fine needle aspirated material from skin lesions and lymph nodes showing numerous intracellular and extracellular, oval, elongated, yeast-like cells dividing by fission. The etiologic agent P. marneffei was isolated in culture from clinical materials in 10 cases when isolation was attempted. All patients were treated with oral itraconazole. All, except one patient, responded favorably to treatment within 7 days. CONCLUSION: Thus, the present cases further confirm the endemicity of penicilliosis marneffei in Manipur and resemble the epidemiology and clinical course of patients from other parts of south-east Asia.

AIDS-Related Opportunistic Infections↗

Studies on solubility and hypoglycemic activity of gliclazide beta-cyclodextrin-hydroxypropylmethylcellulose complexes.

This study was undertaken with an objective to increase the dissolution rate and bioavailability of a poorly water soluble drug gliclazide (Gz) by complexation with beta-cyclodextrin (CD) in the presence of hydroxypropylmethylcellulose (HPMC). Phase solubility studies of Gz were performed in aqueous solutions of different concentrations of CD alone and in the presence of some water soluble polymers. Gz-CD complexes were prepared in 1:1 and 1:2 drug:CD molar ratios by autoclaving, neutralization and kneading methods. The complexes were also prepared in the presence of 0.05% w/w HPMC. Physical mixtures of Gz-CD in 1:1 and 1:2 molar ratios were also prepared. Complexes and physical mixtures were characterized and evaluated for in vitro dissolution in distilled water and hypoglycemic activity in rats. CD enhanced the dissolution of Gz to 1.5 to 2.0 fold. Presence of water soluble polymer HPMC in Gz-CD complexes further enhanced the rate and extent of drug dissolution to 2.5 fold. Gz-CD-HPMC complexes were found to be more promising as they produced not only an early onset but also more intense hypoglycemic effect as compared to pure drug powder and commercial tablets.

Animals↗

Goiter in rural area of Aligarh district.

The survey of iodine deficiency disorder (IDD) and an inquiry about intake of goitrogenic items in two villages of the Aligarh District with a population of 1819 was done. Out of 1152 subjects examined, 348 had goiters but no other abnormality related to the IDD could be found in these subjects. The goiter positivity was 30.2% with visible goiter (grade II & III) rate 8.5%. Six of the subjects had multi nodular goiter of grade III. Urinary iodine levels in 316 of the goitrous subjects were lower (4.939 +/- 1.593 micrograms/dL, M +/- SD, P < 0.001, Median 4.9 micrograms/dL) than 50 urban inhabitants (6.638 +/- 1.372 micrograms/dL). Through in most of the cases (83.9%) T3, T4 and TSH were within normal range, in 35% of the 69 from whom the blood samples were drawn, T3 levels > 150 ng/dL and in 41% of the cases TSH levels > 3.5 mU/L was seen. As in most of the goitrous subjects T3, T4, TSH levels were within normal limits, only iodine deficiency could not be the causative factor for the goiter in 30.2% (severe endemia) of the total population of these two villages. Consumption of millets by the villagers, known to contain goitrogens along with the iodine deficiency in the food and drinking water appears to be responsible for the higher goiter rate in these villagers.

Adolescent↗

Simulation study of the effect of the early mortality exclusion on confounding of the exposure-mortality relation by preexisting disease.

The authors conducted a simulation study to evaluate whether exclusion of the early mortality (deaths occurring during a prespecified period immediately after baseline) reduces confounding of the exposure-mortality relation by preexisting disease. The simulation specified an exposure that decreased mortality risk in the absence of confounding and then introduced confounding by preexisting disease that biased the "true" protective effect of exposure towards greater risk. In 2,000 cohorts, exclusion of the early mortality (deaths occurring during the first 25 months of a 60-month follow-up period) did not alter the mean hazard ratio for exposure under conditions of confounding by preexisting disease that produced a constant, threefold increase in mortality risk during follow-up (the mean hazard ratio was 1.72 for all subjects and 1.72 after exclusion of the early mortality). However, when the authors specified confounding by preexisting disease which produced a threefold increase in mortality risk that attenuated over time, exclusion of the early mortality consistently identified the "true" protective effect of exposure (the mean hazard ratio was 1.07 for all subjects and 0.31 after exclusion of the early mortality). Thus, under conditions of confounding by preexisting disease which produces an increase in mortality risk that attenuates over time--an effect that does have empirical support-the early mortality exclusion can be very effective in revealing the "true" exposure-mortality relation.

Cardiovascular Diseases↗

Validity of a physical activity questionnaire among African-American Seventh-day Adventists.

INTRODUCTION: Physical activity has been identified as an important predictor of chronic disease risk in numerous studies in which activity levels were measured by questionnaire. Although the validity of physical activity questionnaires has been documented in a number of studies of U.S. adults, few have included a validation analysis among blacks. We have examined the validity and reliability of a physical activity questionnaire that was administered to 165 black Seventh-day Adventists from Southern California. METHODS: Subjects completed a self-administered physical activity questionnaire and then "reference" measures of activity (7-d activity recalls, pedometer readings) and fitness (treadmill test) were completed in subsets of this population. RESULTS: The authors found that 7-d recall activity levels correlated well with the corresponding questionnaire indices among women (total activity, r = 0.65; vigorous, r = 0.85; moderate, r = 0.44; inactivity, r = 0.59; sleep duration, r = 0.52) and men (total activity, r = 0.51; vigorous, r = 0.65; moderate, r = 0.53; inactivity, r = 0.69; sleep duration, r = 0.39). Vigorous activity from 7-d recalls was best measured by gender-specific indices that included only recreational activities among men and emphasized nonrecreational activities among women. Correlations between questionnaire data and the other "reference" measures were lower. Test-retest correlations of questionnaire items over a 6-wk interval were high (r = 0.4-0.9). CONCLUSION: Simple questions can measure activities of different intensity with good validity and reliability among black Adventist men and women.

Adult↗

Neurochemical studies on Indian Hypericum perforatum L.

The effect of acute administration of 50% standardised ethanolic extract of Indian Hypericum perforatum (IHp) was studied on the rat brain concentrations of monoamines and their metabolites in five different brain regions, viz. hypothalamus, hippocampus, striatum, pons-medulla and frontal cortex by a HPLC technique. IHp extract was administered at the doses of 50 and 200 mg/kg, p.o. and the brain monoamines were assayed after 30 min of the treatment. IHp treatment significantly decreased the levels of serotonin (5-HT) and its metabolite 5-hydroxy indole acetic acid (5-HIAA) and 5-HT turnover in all the brain regions assayed. On the other hand, IHp treatment significantly augmented the levels of norepinephrine (NE) and its metabolite methylhydroxy phenyl glycol (MHPG) and NE turnover in all the brain regions studied. Similarly, the levels of dopamine (DA) were also significantly augmented in the hypothalamus, striatum and frontal cortex. Likewise, the levels of dihydroxyphenyl acetic acid (DOPAC), the major metabolite of DA, were also increased in these brain areas. Pharmacological studies with IHp extract have shown two major behavioural actions, namely, anxiolytic and antidepressant effects. The present findings tend to rationalise these observations, reduced 5-HT activity being consonant with anxiolytic and increased NA and DA activity being consonant with antidepressant action.

Animals↗

Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L.

A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin.

Analgesics↗

Anti-stress activity of Indian Hypericum perforatum L.

Indian Hypericum perforatum (IHp) was investigated on a 14-day mild, unpredictable and inescapable foot shock stress (FSS) induced perturbations in behaviour (depression), suppressed male sexual behaviour and cognitive dysfunction in albino rats. Gastric ulceration, and adrenal gland and spleen weights, were also used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. FSS induced marked gastric ulceration, significant increase in adrenal gland weight with concomitant decrease in spleen weight. Chronic stress also suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests). All these FSS induced perturbations were attenuated dose dependently by IHp (100 and 200 mg/kg, po) and PG (100 mg/kg, po). The results indicate that IHp has significant anti-stress activity, qualitatively comparable to PG, against a variety of behavioural and physiological perturbations induced by chronic stress, which has been proposed to be a better indicator of clinical stress than acute stress, and may indicate adaptogenic activity.

Animals↗

Variables associated with squamous intraepithelial lesions among women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: To identify factors among women with atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis that are associated with either low grade squamous intraepithelial lesions (LSILs) or high grade squamous intraepithelial lesions (HSILs). STUDY DESIGN: From January 1992 to June 1995, 1,660 women with a diagnosis of ASCUS were followed until the next follow-up appointment after the ASCUS diagnosis. Logistic regression analysis with either LSIL or HSIL at follow-up examination as a dependent variable was done with the following independent variables: patient age, method of follow-up, follow-up time, type of health care coverage and household income. RESULTS: In multivariate analyses, there was a 2.7-fold increase in the odds of LSIL (OR = 2.7, 95% CI = 1.3-5.8) for young women (< or = 25 years), a 2-fold decrease in the odds of LSIL (OR = .5, 95% CI .3-.9) for long time to follow-up (> 18 weeks after ASCUS diagnosis) and an 7.8-fold increase in the odds of LSIL (OR = 7.8, 95% CI = 5.1-11.9) for follow-up by colposcopic biopsy. For the odds of HSIL, there was a 6.8-fold increase (95% CI = 3.2-14.5) for follow-up by colposcopic biopsy as compared to Pap smears and a 3-fold decrease in the odds of HSIL (OR = 3, 95% CI = .1-.7) for high-income women (> $34,857). CONCLUSION: Our findings suggest that among ASCUS patients, younger women and those with shorter follow-up time are more likely to be diagnosed with LSIL. Women with a high income showed a protective association for HSIL. Colposcopic biopsy identified more LSIL and HSIL as compared to repeat Pap smear.

Adult↗

Effect of calcium carbonate on the absorption of levothyroxine.

CONTEXT: The effect of calcium carbonate on the absorption of levothyroxine has not been studied systematically. Such a potential drug interaction merits investigation because concurrent treatment with both drugs is common, particularly in postmenopausal women. OBJECTIVE: To investigate the potential interference of calcium carbonate in the absorption of levothyroxine. DESIGN: Prospective cohort study conducted from November 1998 to June 1999, supplemented with an in vitro study of thyroxine (T(4)) binding to calcium carbonate. SETTING: Veterans Affairs Medical Center in West Los Angeles, Calif. PATIENTS: Twenty patients (age range, 27-78 years; n=11 men) with hypothyroidism who were taking a stable long-term regimen of levothyroxine were included in the study. All patients had serum free T(4) and thyrotropin values in the normal range before beginning the study. INTERVENTION: Subjects were instructed to take 1200 mg/d of elemental calcium as calcium carbonate, ingested with their levothyroxine, for 3 months. MAIN OUTCOME MEASURES: Levels of free T(4), total T(4), total triiodothyronine (T(3)), and thyrotropin, measured in all subjects at baseline (while taking levothyroxine alone), at 2 and 3 months (while taking calcium carbonate and levothyroxine), and 2 months after calcium carbonate discontinuation (while continuing to take levothyroxine). RESULTS: Mean free T(4) and total T(4) levels were significantly reduced during the calcium period and increased after calcium discontinuation. Mean free T(4) levels were 17 pmol/L (1.3 ng/dL) at baseline, 15 pmol/L (1.2 ng/dL) during the calcium period, and 18 pmol/L (1.4 ng/dL) after calcium discontinuation (overall P<.001); mean total T(4) levels were 118 nmol/L (9.2 microg/dL) at baseline, 111 nmol/L (8.6 microg/dL) during the calcium period, and 120 nmol/L (9.3 microg/dL) after calcium discontinuation (overall P=.03). Mean thyrotropin levels increased significantly, from 1.6 mIU/L at baseline to 2.7 mIU/L during the calcium period, and decreased to 1. 4 mIU/L after calcium discontinuation (P=.008). Twenty percent of patients had serum thyrotropin levels higher than the normal range during the calcium period; the highest observed level was 7.8 mIU/L. Mean T(3) levels did not change during the calcium period. The in vitro study of T(4) binding to calcium showed that adsorption of T(4) to calcium carbonate occurs at acidic pH levels. CONCLUSIONS: This study of 20 patients receiving long-term levothyroxine replacement therapy indicates that calcium carbonate reduces T(4) absorption and increases serum thyrotropin levels. Levothyroxine adsorbs to calcium carbonate in an acidic environment, which may reduce its bioavailability. JAMA. 2000;283:2822-2825

Absorption↗

Effect of Indian Hypericum perforatum Linn on animal models of cognitive dysfunction.

The effect of a standardised 50% ethanolic extract of Indian Hypericum perforatum (IHp) was investigated for its putative nootropic activity on various experimental paradigms of learning and memory, viz. transfer latency (TL) on elevated plus-maze, passive avoidance (PA), active avoidance (AA), scopolamine and sodium nitrite induced amnesia (SIA & NIA) in albino rats. Pilot studies indicated that single dose administration of IHp had little or no acute behavioural effects, hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.), once in daily for three consecutive days, while piracetam (500/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard drug. Control rats were treated with equal volume of vehicle (0.3% carboxymethyl cellulose (CMC)). IHp and piracetam when given alone shortened the TL on day 1, 2, 9 and also antagonised the amnesic effects of scopolamine and sodium nitrite on the TL significantly. IHp had no significant per se effect on the retention of the PA in rats. Only the higher dose (200 mg/kg, p.o.) produced a significant reversal of scopolamine induced PA retention deficit but no significant reversal was observed with sodium nitrite. Piracetam showed significant per se facilitatory effect on PA retention and also reversed the scopolamine and sodium nitrite induced impaired PA retention. In the AA test, IHp in both the doses, and piracetam, facilitated the acquisition and retention of AA in rats and the IHp effects were found to be dose dependent. Both the doses of IHp and piracetam significantly attenuated the scopolamine and sodium nitrite induced impaired retention of AA. These results indicate a possible nootropic action of IHp, which was qualitatively comparable with that induced by piracetam.

Amnesia↗

Transmission of HIV from injecting drug users to their wives in India.

We aimed to identify factors associated with transmission of human immunodeficiency virus (HIV) from injecting drug users (IDUs) to their wives in Manipur, northeast India, where the prevalence of HIV among IDUs is 80% via a case-control study. One hundred and sixty-one HIV-infected IDUs and their wives were recruited from September 1996 to August 1997 inclusive. HIV status was determined by enzyme-linked immunosorbent assay (ELISA) plus Western blot, Interviews were administered anonymously. Regression analysis identified factors associated with transmission of HIV from IDU husbands to their non-injecting wives. Seventy-two wives (45%) were HIV-positive. Only 15% of the couples reported regular usage of condoms during intercourse. On multivariate analysis, a sexually transmitted disease (STD) in either member, reported by the husband, estimated duration of HIV in the husband for >8 years, and a history of blood transfusions were associated with infection in the wife. In conclusion, STDs are associated with transmission of HIV from husband to wife. Improved control of STDs, condom promotion, and improved blood screening are urgently needed in Manipur.

Case-Control Studies↗

Animal experimentation: a rational approach towards drug development.

Man's observation of animals as objects of study undoubtedly began in prehistoric times. The first recorded attempt involving the use of live animals for research was by Ersistratis in Alexandria in 300 B.C. Animal investigation has clearly made possible the enormous advances in drug development in this century. A cursory review of any modern text book of pharmacology or medicine will attest the many drugs currently available to benefit mankind in the struggle to eradicate and control diseases. The main purpose of this article is to describe some of the experimental work on animals which contributed to the discovery and development of drugs benefiting human beings and other animal species. Since animal experimentation has occupied a focal position in all the research leading to useful drugs, one will appreciate that it will be necessary to limit the discussion to certain aspects of this broad and interesting topic. With this in mind, an attempt is made to relate briefly the nature of animal investigations which were instrumental in the development of major classes of drugs. Some attention has also been focused on legislation's on animal experimentation of some developed countries with emphasis on India and to views on animal experimentation. We hope this article will stimulate the minds of the scientists for a rational debate on the future of animal experimentation.

Animal Rights↗