Swiss Strain Research Articles

Virulence of in vivo and in vitro produced conidia of Metarhizium brunneum strains for control of wireworms

Wireworms are the soil inhabiting larvae of click beetles and can cause severe damage to arable crops such as potatoes (Solanum tuberosum, L.). Several strains of the entomopathogenic fungus Metarhizium brunneum (Petch) are pathogenic to wireworms. In this study, three European strains of M. brunneum were tested in the laboratory against the most damaging wireworm species in Europe, Agriotes lineatus (L.), Agriotes obscurus (L.) and Agriotes sputator (L.). A Swiss strain, isolated from an A. obscurus cadaver, proved to be most effective, killing up to 73% of A. lineatus and 83% A. obscurus individuals, respectively. The median lethal time (LT50) was 21 days post inoculation (dpi) for A. lineatus and 14 dpi for A. obscurus. The strain did not lose virulence through subsequent cultivation on artificial medium and thus seems to be suitable for mass production as a biocontrol agent for wireworm control.

Raloxifene preserves phenytoin and sodium valproate induced bone loss by modulating serum estradiol and TGF-β3 content in bone of female mice

Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on PHT and SVP-induced alterations in bone in mice and to unravel the role of estradiol and TGF-β3 in mediation of bony effects by either AEDs or raloxifene. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female mice were treated with PHT (35mg/kg, p.o.) and SVP (300mg/kg, p.o.) for 120days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and therapeutic treatment with raloxifene ameliorated bony alterations and was more effective than CVD. It also significantly restored estradiol and TGF-β3 levels. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with antiepileptic efficacy of these drugs, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Phenytoin and sodium valproate but not levetiracetam induce bone alterations in female mice.

Adverse effects on the bone are amongst the potentially adverse clinical consequences with antiepileptic drugs (AEDs). This study compared the effects of 3 AEDs (phenytoin (PHT), sodium valproate (SVP), and levetiracetam (LTM)) on the bones of a Swiss strain of albino female mice. Drugs were administered daily for 4 months at doses that produced plasma concentrations corresponding to the clinically relevant therapeutic ranges. PHT and SVP (but not LTM) significantly lowered the bone mineral density (BMD) of lumbar vertebrae (L2-L4) as evaluated by dual-energy X-ray absorptiometry (DEXA) scan. The findings were supported by histopathology of vertebral (lumbar) bone and analysis of bone turnover markers. While both PHT and SVP reduced alkaline phosphatase (ALP) and hydroxyproline (HxP) in lumbar vertebrae, and elevated tartarate-resistant acid phosphatase (TRAP) and urinary excretion of calcium, LTM did not affect any of these markers of bone turnover, indicating that the drug might be a safer option in female epileptic patients prone to bone changes.

2.45-GHz microwave irradiation adversely affects reproductive function in male mouse, Mus musculus by inducing oxidative and nitrosative stress

Electromagnetic radiations are reported to produce long-term and short-term biological effects, which are of great concern to human health due to increasing use of devices emitting EMR especially microwave (MW) radiation in our daily life. In view of the unavoidable use of MW emitting devices (microwaves oven, mobile phones, Wi-Fi, etc.) and their harmful effects on biological system, it was thought worthwhile to investigate the long-term effects of low-level MW irradiation on the reproductive function of male Swiss strain mice and its mechanism of action. Twelve-week-old mice were exposed to non-thermal low-level 2.45-GHz MW radiation (CW for 2 h/day for 30 days, power density = 0.029812 mW/cm2 and SAR = 0.018 W/Kg). Sperm count and sperm viability test were done as well as vital organs were processed to study different stress parameters. Plasma was used for testosterone and testis for 3β HSD assay. Immunohistochemistry of 3β HSD and nitric oxide synthase (i-NOS) was also performed in testis. We observed that MW irradiation induced a significant decrease in sperm count and sperm viability along with the decrease in seminiferous tubule diameter and degeneration of seminiferous tubules. Reduction in testicular 3β HSD activity and plasma testosterone levels was also noted in the exposed group of mice. Increased expression of testicular i-NOS was observed in the MW-irradiated group of mice. Further, these adverse reproductive effects suggest that chronic exposure to nonionizing MW radiation may lead to infertility via free radical species-mediated pathway.

Cold growth behaviour and genetic comparison of Canadian and Swiss Listeria monocytogenes strains associated with the food supply chain and human listeriosis cases

Sixty-two strains of Listeria monocytogenes isolated in Canada and Switzerland were investigated. Comparison based on molecular genotypes confirmed that strains in these two countries are genetically diverse. Interestingly strains from both countries displayed similar range of cold growth phenotypic profiles. Based on cold growth lag phase duration periods displayed in BHI at 4 °C, the strains were similarly divided into groups of fast, intermediate and slow cold adaptors. Overall Swiss strains had faster exponential cold growth rates compared to Canadian strains. However gene expression analysis revealed no significant differences between fast and slow cold adapting strains in the ability to induce nine cold adaptation genes (lmo0501, cspA, cspD, gbuA, lmo0688, pgpH, sigB, sigH and sigL) in response to cold stress exposure. Neither was the presence of Stress survival islet 1 (SSI-1) analysed by PCR associated with enhanced cold adaptation. Phylogeny based on the sigL gene subdivided strains from these two countries into two major and one minor cluster. Fast cold adaptors were more frequently in one of the major clusters (cluster A), whereas slow cold adaptors were mainly in the other (cluster B). Genetic differences between these two major clusters are associated with various amino acid substitutions in the predicted SigL proteins. Compared to the EGDe type strain and most slow cold adaptors, most fast cold adaptors exhibited five identical amino acid substitutions (M90L, S203A/S203T, S304N, S315N, and I383T) in their SigL proteins. We hypothesize that these amino acid changes might be associated with SigL protein structural and functional changes that may promote differences in cold growth behaviour between L. monocytogenes strains.

Evaluation of analgesic activity of perindopril in albino mice.

The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain) weighing 25-30 g were allocated to each experimental model and in each model there were three groups. The control group received normal saline (25 ml/kg) per orally, standard group received pentazocine (10 mg/kg) intra-peritoneal and test groups received perindopril (1 mg/kg) per orally. Perindopril and normal saline was administered 2 h before, whereas the pentazocine was administered 15 min prior to Eddy's hot plate, writhing and tail clip methods. The decrease in number of writhes, the delay in reaction time in tail clip and Eddy's hot plate method denoted the analgesic activity. Perindopril decreased the number of writhes, delayed the reaction time in tail clip and Eddy's hot plate method considerably when compared with control (normal saline), but less when compared with standard (pentazocine). Perindopril exhibits analgesic activity in thermal, chemical, and mechanical pain models in albino mice.

Acute and sub‑chronic toxicity study of Brahmi ghrita in rodents

Context: Brahmi Ghrita (BG) contains Brahmi (Bacopa monneri), Vacha (Acorus calamus), Kushtha (Saussurea lappa), Shankhapushpi (Convolvulus pluricaulis) and Puran Ghrita, mentioned for treatment of various diseases. Aim: To assess acute and sub‑chronic toxicity of Brahmi Ghrita in mice and rats, respectively. Materials and Methods: In acute toxicity study, Swiss strain albino mice were administered orally Brahmi Ghrita doses of 1, 2.5 and 5 g/kg and observed for behavioural changes and mortality, if any. In sub chronic toxicity study, Charles Foster albino rats were administered two doses of Brahmi Ghrita i.e., 400 and 800 mg/kg, p.o. for 30 consecutive days. During 30 days of treatment, rats were observed for any changes in body weight and daily food and water intake. After 30 days, rats were sacrificed for haematological, biochemical and histopathology study. Result: There was no mortality or abnormal behaviour, observed in acute toxicity study in mice at all the three dose levels. In sub‑chronic toxicity study, Brahmi Ghrita did not produce any significant changes in body weight and daily food and water intake of rats when compared to control group rats. Further, haematological and biochemical parameters were also found normal. Histopathological study revealed normal architecture of kidney and liver of Brahmi ghrita treated rats. Conclusion: Brahmi Ghrita is safe in rodent and mice. Key words: Acute toxicity, Brahmi ghrita, sub chronic toxicity

EFFECT OF CALCUSOLTM ON CuZnSOD EXPRESSION IN MICE RENAL OF NEPHROLITHIASIS MODEL

This study aimed to determine the effect of traditional medicine, CalcusolTM, on number of cells expressing CuZnSOD in mice renal of nephrolithiasis model. Eight weeks old Swiss strain male mice (Mus musculus) were divided into five groups: (A) control, (B) nephrolithiasis, (C) CalcusolTM, (D) nephrolithiasis & CalcusolTM, and (E) nephrolithiasis & CalcusolTM simultaneously. Nephrolithiasis was induced by applying porang tuber (Amor- phophallus muelleri) flour 0.06 mg/g of body weight during 3 months. CalcusolTM is traditional medicine, made of tempuyung leaves extract with Saccharum lactis as additional substance. The dosage for CalcusolTM treatment was 3.3 mg/g of body weight. After 3 months treatment, the mice were killed by neck-dislocation, the kidneys were isolated and prepared for paraffin histology. CuZnSOD was analyzed by immunohistochemistry (IHC), using rabbit policlonal antibody anti-SOD1 (Bioss, bs-1079R) as primary antibody. Tissues were observed under Olympus BX51, 400x mag- nification. Images were documented with Olympus Digital Camera DP20. The histology images were analized in Immunoratio software online (URL: http://153.1.200.58:8080/immunoratio/) to receive the percentage of number of cells expressing CuZnSOD. The result showed that CalcusolTM administration could decrease number of cells expressing CuZnSOD in kidney significantly (P<0.05). It was supposed that antioxidant content in CalcusolTM could scavenge ROS directly with no induction of CuZnSOD production in cell.

Eclipta alba ameliorates carbon tetrachloride-induced structural and functional changes in liver of mice

The aim of the present investigation was to evaluate the ameliorative effect of Eclipta alba extract against carbon tetrachloride (CCl4)–induced structural and functional changes in livers of mice. Healthy adult Swiss strain female albino mice were orally administered with CCl4 (826 mg/kg body weight/day, p.o.) alone and along with Eclipta alba extract (100, 200 and 300 mg/kg body weight/day, p.o.) for 30 days. The degree of protection was determined by measuring histopathological changes and lipid peroxidation in liver as well as activities of ALT, AST, ACP, ALP, LDH, γ-GT enzymes and bilirubin contents in serum of mice. The histopathological studies revealed severe necrosis, fatty infiltration, lymphocytic infiltration and fibrosis in liver of CCl4 treated mice. In addition, biochemical studies revealed a significant increase in lipid peroxidation. The enzymes activities as well as bilirubin contents in serum were significantly (p<0.05) increased in CCl4 only treated mice when compared with the control group. However, co-treatment of CCl4 along with Eclipta alba extract showed significant reductions in activities of enzymes and bilirubin content as compared with CCl4 alone treated mice. The effects were dose-dependent (r = 0.9826 to 1). Carbon tetrachloride induced lipid peroxidation was significantly (p<0.05) ameliorated in a dose-dependent manner. Histopathological changes were also ameliorated on treatment with Eclipta alba extract. The ameliorative effects of Eclipta alba on CCl4–induced hepatotoxicity could be due to its antioxidative property. The extract was found to be safe as evidenced by their high LD50.

Toxicopathological and biochemical effects of Carbon Tetrachloride CCl4 with residual accumulation in Liver of mice

Objective :- The aims of the present study are to determine the toxicopathological and pathophysiological effects of carbon tetrachloride (CCl4), with measurement residual quantity of CCl4 in liver tissue by (HSGC) method. Methodology :- 40 Swiss strain white mice were used, average weigh about 30 –32 g , divided into three groups, the T1 and T2 group were administrated with (100 and 200 mg/kg/body weight CCl4 respectively , given via intraperitoneal injection two does weekly for 40 day). While the 3rd group served as control. Clinical signs were reported during the course of the study, then at day 40 post treatment , all animal were sacrificed, blood were collected at 20 and 40 days of treatment period for biochemical test and post mortem examination was done and any gross lesions were reported, liver section was taken for pathophysiological examination, also for measurement residual accumulated in tissue by Head-Space Gas Chromatographic analysis (HSGC) method. Results :- All results showed that CCl4 caused significant increase of serum alanine aminotransferase and aspartate aminotransferase activity. Histopathological picture of liver, showed damage of liver parenchyma, disappear arrangements of hepatocyte, loss of hepatic cord, with congestion and dilatation of blood vessel also coagulative necrosis and apoptotic cells. Infiltration of inflammatory cells (macrophages &lymphocyte). Also high quantity from CCl4 was residual in hepatic tissue. Conclusion :- The present study investigated that the CCl4 affected on the liver tissue, and causes histopathological lesion with elevation of liver enzymes specially ALT& AST , with accumulative effect in liver tissue after measurement by GC system. And the degree of influence depended on the concentration of the toxic dose .

The Oxidative Response of Mouse Hearts is Modulated by Genetic Background

Smoking plays an important role in cardiovascular diseases. However, the reasons why some individuals develop those diseases and others do not remain to be explained. This study aimed at assessing the redox profile of the heart of different mouse strains after exposure to cigarette smoke. Male mice of the Swiss (n = 10), C3H (n = 10), BALB/c (n = 10) and C57BL/6 (n = 10) strains were exposed to cigarette smoke (12 cigarettes/day), while their respective controls (n = 10) were exposed to ambient air for 60 days. After being euthanized, their heart was removed for biochemical analyses. Although the malondialdehyde content did not increase in any of the groups, catalase activity decreased in the Swiss (p < 0.05) and BALB/c (p < 0.05) strain mice as compared with their respective control groups, while myeloperoxidase decreased in the C3H (p < 0.05) and C57BL/6 (p < 0.001) strain mice as compared with their respective control groups. The reduced glutathione content decreased in the Swiss, C3H, C57BL/6 (p < 0.05) and BALB/c (p < 0,001) strain mice as compared with their respective control groups. Regarding reduced glutathione content, an increase was observed in the Swiss strain mice (p < 0.05), while a decrease was observed in the C3H (p < 0.05) and BALB/c (p < 0.001) strain mice as compared with their respective control groups. The reduced glutathione/reduced glutathione ratio showed a reduction in the Swiss and C57BL/6 (p < 0.05) strain mice as compared with their respective control groups. The genetic background of mice can influence the antioxidant response after exposure to cigarette smoke and seems to be a determinant factor for redox imbalance in Swiss and C57BL/6 strain mice. Understanding antioxidant responses and genetic background of C3H and BALB/c strain mice might provide important information regarding cardiac resistance to cigarette smoke.

Testing the efficacy of quercetin in mitigating bisphenol A toxicity in liver and kidney of mice

Quercetin (3,5,7,3',4'-pentahydroxy flavone) is a potent antioxidant found in various fruits and vegetables. The present investigation was an attempt to evaluate the mitigatory effect of quercetin on the damage caused by bisphenol A (BPA; 2,2-bis (4-hydroxyphenyl) propane), a well-known xenoestrogen, on liver and kidney of mice. Swiss strain adult male albino mice were orally administered with 120 and 240mg/kg body weight (bw)/day BPA with or without quercetin (60mg/kg bw/day) for 30days. On the completion of the treatment period, animals were killed; organs were isolated and used for the study. Results revealed that oral administration of BPA for 30days caused significant and dose-dependent decrease in body weight. Absolute and relative organ weights, total lipid and cholesterol contents were significantly increased in liver and kidney of mice when compared with vehicle control. BPA treatment also caused, when compared with vehicle control, a statistically significant reductions in the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as in glutathione and total ascorbic acid contents; however, significant increase was found in malondialdehyde (MDA) levels. Histopathological studies revealed hepatocellular necrosis, cytoplasmic vacuolization and decrease in hepatocellular compactness in liver as well as distortion of the tubules, increased vacuolization, necrosis and disorganization of glomerulus in the kidney of BPA-treated mice. All these effects were dose-dependent. Co-treatment with quercetin (60mg/kg bw) and BPA (low dose and high dose) alleviates the changes in body weight, as well as absolute and relative organ weights of mice. It also ameliorates the oxidative stress created by BPA by lowering MDA levels and by increasing enzymatic and nonenzymatic antioxidants as well as it brings back the normal histoarchitecture of liver and kidney of mice. The present results revealed that graded doses of BPA caused oxidative damage in liver and kidney of mice, which is mitigated by quercetin.

Toxicopathological effects of lead acetate on the brain of male mice

The aim of the present study is to determine the influence of different doses of lead acetate on the central nerves system. 25 Swiss strain white mice were used, each weighing about 30 –32 g, divided into three groups, first group (n=10) treated with 0.5 ml. contain 150 mg/kg/body weight lead acetate via stomach tube daily for 40 days, second group (n=10) treated with 0.5 ml. contain 300 mg/kg/body weight lead acetate via stomach tube daily for 40 days. While the third group (n=5) served as control and were given mammalian physiological saline. Clinical signs were reported during the course of the study, then at day 40 post treatment , all animal were sacrificed and post mortem examination was done and any gross lesions were reported, then the pieces of brain was fixed in 10% formalin for 72 hours .The pathological results showed congestion of cerebellum and cerebrum of both treated group but the 2nd group was more sensitive. Histopathological examination of 1st group expressed moderate pathological lesions, characterized by extracellular edema around neuron cells and Virchow Robbin space , as well as proliferation of astrocyets in the white matter , also central chromatolysis of neurons and Nissle granules with homogenous pink their cytoplasm in 1st G. while in 2nd G the main lesions characterized by severe congestion of blood vessels with inflammatory cells infiltration in the lumen of arachnoids' space and brain parenchyma as well as hemorrhage with aggregation of microglia in the wall of blood vessels which characterized by round shape and clear cytoplasm (microgliosis). Also severe neuron degeneration, with Alzheimer's type-II astrocyets are reported in other animals characterized by pairs observed surrounded by clear space. And there is no clear pathological lesion in control group.In conclusion the present study investigated that the lead acetate affected on the brain tissue, and the degree of influence depended on the concentration of the toxic dose.

Exploration par le système ISAC des manifestations d’allergie alimentaire aux aliments végétaux chez l’adulte

Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disorder caused by mutationally altered dominant-acting sarcomere proteins, exhibits significant clinical heterogeneity. To determine whether genetic background could influence the expression of this disease, we studied a murine model for this human condition. Hypertrophic responses to the Arg403Gln missense mutation in a cardiac myosin heavy chain gene were compared in 129SvEv (inbred; designated 129SvEv-α MHC403/+) and Black Swiss (outbred; designated BSw- α MHC403/+) strains. At 30–50 weeks of age all 129SvEv- α MHC403/+showed left ventricular hypertrophy, while left ventricular wall thickness was increased in only half of BSw- α MHC403/+mice demonstrating that a polymorphic modifier gene can determine the hypertrophic response to this dominant-acting sarcomere protein mutation. Further analysis suggests that SJL/J mice bear a recessive allele of this modifier gene that prevents a hypertrophic response to the Arg403Gln missense mutation. We conclude that genetic modifiers in mice, and presumably in man, can alter the hypertrophic response to sarcomere protein gene missense mutations.

Emergence of Canine Distemper Virus Strains With Modified Molecular Signature and Enhanced Neuronal Tropism Leading to High Mortality in Wild Carnivores

An ongoing canine distemper epidemic was first detected in Switzerland in the spring of 2009. Compared to previous local canine distemper outbreaks, it was characterized by unusually high morbidity and mortality, rapid spread over the country, and susceptibility of several wild carnivore species. Here, the authors describe the associated pathologic changes and phylogenetic and biological features of a multiple highly virulent canine distemper virus (CDV) strain detected in and/or isolated from red foxes (Vulpes vulpes), Eurasian badgers (Meles meles), stone (Martes foina) and pine (Martes martes) martens, from a Eurasian lynx (Lynx lynx), and a domestic dog. The main lesions included interstitial to bronchointerstitial pneumonia and meningopolioencephalitis, whereas demyelination--the classic presentation of CDV infection--was observed in few cases only. In the brain lesions, viral inclusions were mainly in the nuclei of the neurons. Some significant differences in brain and lung lesions were observed between foxes and mustelids. Swiss CDV isolates shared together with a Hungarian CDV strain detected in 2004. In vitro analysis of the hemagglutinin protein from one of the Swiss CDV strains revealed functional and structural differences from that of the reference strain A75/17, with the Swiss strain showing increased surface expression and binding efficiency to the signaling lymphocyte activation molecule (SLAM). These features might be part of a novel molecular signature, which might have contributed to an increase in virus pathogenicity, partially explaining the high morbidity and mortality, the rapid spread, and the large host spectrum observed in this outbreak.

Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis

Visceral toxocariasis is a serious public health problem with a cosmopolitan distribution. Children are susceptible due to their immature immune system and high risks of infection. Nevertheless, the few completed studies about immunosuppression have had controversial results. To evaluate the effect of two immunosuppressive drugs on the larval burden of Toxocara canis, four groups of ten Swiss strain mice each were inoculated on day0 with 1,200 embryonated T. canis eggs. Fifteen days before the experimental infection, group 1 (control) was treated via intraperitoneal injection (IP) with sterile distilled water and groups 2 and 3 were treated with dexamethasone (DEX) at 1 and 5mg/kg/day, respectively. Additionally, group 4 was treated IP with cyclophosphamide (CY) at 50mg/kg at two times per week for 2weeks. Sixty days following infection, the mice were euthanised to recover the larvae by means of the tissue digestion technique. The levels of antibodies detected by indirect ELISA were not associated with the larval burden. Administration of CY (50mg/kg) and DEX (5mg/kg) resulted in an increase of the larval burden of 162.1% and 50.8%, respectively, in relation to the control group. These two treatments, especially CY (50mg/kg), promoted immunosuppression and the establishment of a significant larval burden, supporting its further utilisation in studies related to immunosuppression in visceral toxocariasis.

Covering the Cover

Covering the Cover

Age and strain differences in the rat of development of functional tolerance to ethanol by mice.

Abstract The time course of development of functional tolerance to ethanol was investigated in mice during the inhalation of ethanol vapour, using loss of righting reflex as the behavioural end-point. In male mice of the TO Swiss strain, weanling mice (18 days) showed no development of tolerance during continuous or repeated exposure to ethanol vapour for 6 h. Adolescent TO Swiss mice (35–40 days) showed rapid development of functional tolerance, reaching a state where 2x the original effective concentration of ethanol in blood was required to produce loss of righting reflex within 5 h. Older adult mice (150–200 days) showed some development of tolerance during continuous or repeated exposure to ethanol for 5 h but this was much less than that seen in adolescent mice. When adolescent males of the C57BL, TO Swiss and DBA2 strains were compared, marked differences were observed. C57BL mice showed very rapid development of functional tolerance to ethanol in which more than 2 × the original effective dose was required to produce loss of righting reflex after about 3 h of ethanol exposure. TO Swiss mice showed somewhat slower development of ethanol tolerance. DBA2 mice showed little evidence of development of functional tolerance over the time course of these experiments. Evidence was also obtained that similar age and strain differences may exist with respect to tolerance to the hypothermic effects of ethanol. These results are discussed in relation to current concepts of ethanol sensitivity, tolerance and physical dependence.

Functional tolerance to ethanol in mice: relationship to lipid metabolism

Abstract The development of functional tolerance to ethanol was studied in young adult mice of the TO Swiss and C57BL strains. Ethanol administration was by intermittent inhalation for 7 h and the development of tolerance was assessed by estimating blood ethanol concentrations at successive losses of the righting reflex. The administration of (±)α-tocopherol at a dose previously shown to inhibit the effect of ethanol on peripheral phospholipid composition (750 mg kg−1 i.p.) was without effect on functional tolerance. Chronic administration of DL-carnitine, 7% w/w in diet for 10 days, a treatment previously shown to prevent ethanol-induced triglyceride accumulation, was also without effect on ethanol tolerance. Administration of the cholesterol synthesis inhibitor, diazacholesterol (30 mg kg−1 i.p.) 3 times per week for 3 weeks from weaning, markedly inhibited the subsequent development of functional tolerance. Administration of the inhibitor of protein synthesis, cycloheximide (300 μg kg−1 i.p.) greatly inhibited the development of ethanol tolerance whereas actinomycin D (100 μg kg−1 i.p.) was without effect. The results are discussed in relation to the hypothesis that ethanol cellular tolerance results from adaptation in the composition of the lipids of neuronal membranes. It is concluded that synthesis of some protein is involved in the development of cellular tolerance and also that cholesterol plays some part in the development of tolerance.

Acute and sub-chronic toxicity study of standardized extract of Fumaria indica in rodents

Despite Fumaria indica (FI) widespread medicinal uses in the Indian traditional medicine, no systematic study of the potential toxicity of the plant has been described. To assess acute and sub-chronic toxicity of a 50% ethanolic extract of FI in mice and rats respectively. In acute toxicity study, Swiss strain albino mice of either sex were administered orally FI doses of 1, 2.5 and 5 g/kg and observed for behavioural changes and mortality, if any. In sub-chronic toxicity study, Charles Foster albino rats of either sex were administered two doses of FI i.e., 100 and 400mg/kg, p.o. for 30 consecutive days. During 30 days of treatment, rats were observed for any change in body weight and daily food and water intake. After 30 days, rats were sacrificed for haematological, biochemical and histopathology study. Control animals were administered 0.3% carboxymethyl cellulose (CMC) suspension by oral route. There was no mortality or abnormal behaviour, observed in acute toxicity study in mice at all the three dose levels. In sub-chronic toxicity study, FI did not produce any significant change in body weight and daily food and water intake of rats when compared to vehicle treated rats. Further, haematological and biochemical parameters were also found normal. Histopathological study revealed normal architecture of kidney and liver of FI treated rats. FI extract, provisionally standardized on its fumarate contents, seems to fulfill a preclinical criterion necessary for its further development as a clinically useful adaptogen.