Activating mutations in KRAS gene cause constitutively active Ras GTPase, which leads to over-activation of downstream Raf/Erk/Map kinase and other signaling pathways, resulting in cell transformation and tumorigenesis (Fig 1) (2),(3). KRAS mutations are present in approximately 30% to 50% of colon cancer specimens (4).

Fearon and Vogelstein established a stepwise hypothesis for colorectal cancer tumorigenesis and delineated the importance of mutation in Inhibitors,research,lifescience,medical RAS gene as an initiating event in the formation of malignant tumor (5). Figure 1 Epidermal growth factor receptor signal transduction pathway. * Common sites of mutation in colorectal cancer. Preclinical studies have suggested that constitutively activated selleck chemicals mutant KRAS can promote tumor invasion and metastasis by stimulating matrix metalloproteases, cysteine proteases, serine proteases, and urokinase plasminogen activator that facilitate migration through the basement membrane (6),(7),(8). Despite such findings the Inhibitors,research,lifescience,medical role of KRAS mutation in prognosis of mCRC patients is not clear. The RASCAL study, which was the largest study designed to analyze the prognostic value

of KRAS status showed that a glycine-to-valine mutation in codon 12 increased the likelihood of disease relapse and a lower overall survival (OS) (9). Multiple other studies with smaller sample size did Inhibitors,research,lifescience,medical not demonstrate any impact

of KRAS mutations on survival (10),(11),(12). Even in the updated RASCAL II study, the evidence of a statistically significant worse clinical outcome was limited to stage III disease and was not confirmed for other stages (13). Inhibitors,research,lifescience,medical These results are limited by their retrospective nature and lack of adequate power to detect significant differences. The relationship between KRAS status of primary tumor and stage at diagnosis as well as pattern of spread is also not clear. Samowitz et al. reported that codon 12 mutations in KRAS gene were found to be much more common in proximal tumors and were associated Inhibitors,research,lifescience,medical with advance stage at presentation (14). Bazan and colleagues showed PDK4 that codon 12 mutation in tumor was associated with mucinous histology and mutation in codon 13 was associated with advanced Duke stage (15). In a retrospective study KRAS mutation of the primary tumor was also associated with higher incidence of metastatic disease to lungs (16). Analysis of KRAS and BRAF mutation status in PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer revealed that incidence of either mutation was not significantly different according to tumor stage. KRAS mutation was associated with grade of the tumor, while BRAF mutation was associated with right-sided tumors, older age, female gender, high grade, and MSI-high tumors.

Conventional and tissue Doppler echocardiography

Two groups were echocardiographically examined in the left-lateral position by using a iE33 machine (Philips, Amsterdam, the Netherlands). According to the biplane Simpson’s rule, LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) in mL and EF% were defined.13) Inter ventricular septum (IVS) thickness was measured (in mm) during systole. LV wall thickness was also measured (in mm). Left ventricular mass and its Inhibitors,research,lifescience,medical indexed value was assessed by the method proposed by Devereux et al.10) Left atrial (LA) volume in systole was also measured just before the mitral valve opening, using the biplane Simpson’s method, as a mean between the values recorded in apical four- and two-chamber approaches. Subsequently, LAV was indexed for BSA, such as LAVI in mL/m2.14) Finally, MPI was evaluated by using TDE method. Pulsed-wave TDE was performed by activating the

Inhibitors,research,lifescience,medical tissue Doppler function. Sample volume was placed at the lateral annular mitral site in apical four chamber view, in order to record the following cardiac time intervals: iso-volumetric contraction time (IVCT) in ms; iso-volumetric relaxation time (IVRT) in ms; and ejection Inhibitors,research,lifescience,medical time (ET) in ms. Images were acquired with a variable frequency phased-array transducer. The filter settings were kept low, and gains were adjusted to the minimal optimal level to minimize noise and eliminate the signals produced by the transmitral flow. Three consecutive beats were measured and averaged for each parameter at a sweep speed of 100 mm/s. MPI was defined as the sum of IVCT and IVRT divided by ET.15) LAVI; MPI; IVCT; IVRT; and ET were defined in controls (group I) too, as reference values (Table 3). Table Inhibitors,research,lifescience,medical 3 LAVI, time intervals and MPI-TDE values in two groups Statistical analysis Echocardiographic data are presented as a mean values ± SD. Statistical analyses

were performed with SPSS statistical software (SPSS, Chicago, IL, USA). www.selleckchem.com/products/co-1686.html Differences Inhibitors,research,lifescience,medical between two groups were examined by an unpaired t test. A p value < 0.05 was considered significant. Finally, LAVI was compared to MPI, IVCT, IVRT and ET between controls (group I) and hypertensive patients (group II) by unpaired t-test. Results Mean values of LVEDV and LVESV were 95 ± 18 mL and 39 ± 17 mL respectively in controls (group I). These resulted 125 ± 15 mL (LVEDV), and 48 ± 11 mL (LVESV) in hypertensive about patients (group II). Differences were significant (p < 0.05). IVS thickness was = 10 ± 0.4 mm in controls, it resulted 135 ± 0.5 mm in hypertensive-patients. Mean value of E/A waves ratio was 1.21 ± 0.38 in normal and 0.85 ± 0.27 in hypertensives (p < 0.01). Mitral deceleration time (DT) resulted = 135 ± 3.4 ms in healthy adults and 245 ± 31 in hypertensive patients (p < 0.01). On the other hand, LV walls’ thickness was 9 ± 0.3 mm in controls (group I) and 17 ± 0.2 mm in hypertensives (group II). Differences were significant (p < 0.

The hypothetical model of APP processing involves mobilization of β-CTF. However, the transport mechanism of β-CTF between nonraft and raft domains remains to be elucidated;

resolving this issue would provide a basis for the identification of new therapeutic targets for AD. Acknowledgments We thank Michael Farzan for BACE1 cDNA. This work was supported by a Grant-in-Aid for Scientific Research (C) Inhibitors,research,lifescience,medical from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and by grants from the Ministry of Health, Labor, and Welfare, Japan. The authors all state that there are no conflicts of interests with the research presented in this paper.
Leprosy, a disease known for its characteristic insensitive skin patches, is the main cause of peripheral neuropathy in endemic countries. Neuropathy is often clinically silent in its evolution making Inhibitors,research,lifescience,medical early diagnosis exceptionally challenging so that even highly skilled clinical management may not be able to prevent permanent

nerve damage (Job 1989). The Enhanced Global Strategy for 2011–2015 emphasizes the goal of reducing the number of patients with Inhibitors,research,lifescience,medical permanent disabilities, which in 2009 totaled 14,320 new patients (WHO 2010). Fortunately, crucial information concerning the etiology, incidence, risk factors, and treatment of peripheral neuropathy is becoming more and more readily available despite the fact that many key questions regarding early diagnosis and prevention strategies continue unanswered. Clinical neurological examination, especially of sensory function, is essentially subjective in that it is based on a certain level of patient awareness. Accordingly, distinct techniques aiming toward a more objective Inhibitors,research,lifescience,medical detection of early nerve function impairment (NFI), imperative for successful therapeutic interventions, have been developed and tested (Van Brakel et al. 2007). Nerve conduction study (NCS) Inhibitors,research,lifescience,medical provides reliable information regarding large GSK2606414 myelinated nerve fiber (LNF) impairment, often a late event in leprosy

(Anthia et al. 1975). However, a special approach click here is required to detect impairment of the small, nonmyelinated and poorly myelinated fibers that are so, particularly vulnerable to early damage from the Mycobacterium leprae (M. leprae)-induced inflammatory infiltrate (Rambukkana 2000). Specifically, autonomic abnormalities can be effectively studied by measuring the skin vasomotor reflex (SVMR) (Low et al. 1983) and the sympathetic skin response (SSR) (Shahani et al. 1984). Leprosy neuropathy is complex, with the superposition of acute and chronic sensory, motor and/or autonomic events (Charosky and Cardama 1983). A prospective clinical study was performed in newly diagnosed leprosy patients to evaluate the small and large myelinated fibers by means of clinical neurological examination and neurophysiological studies.

In this issue of the journal, the study reported by Chen and colleagues (6) adds an interesting new dimension. Using the HT29 colon cancer cell line, the authors show that the addition of high-dose insulin in the presence of oxaliplatin was associated with Akt activation and chemoresistance, effects which were reversed by the use of a PI3K

inhibitor. The reductionist approach and simplicity of the preclinical experiments renders these data preliminary but certainly thought provoking. Furthermore, given the mixed clinical observations summarized in the opening paragraph, Inhibitors,research,lifescience,medical the reader may well ask, are these findings clinically relevant? The answer is simple Inhibitors,research,lifescience,medical at one level – obesity is a heterogeneous condition – and complex at many more levels. It is well known that serum insulin levels increase with increasing BMI, but despite this good correlation, as shown in Figure 1, there is wide variability. Increasingly, the metabolic literature recognizes that obesity may be dichotomized into metabolically benign and malign states defined by criteria of insulin resistance, subclinical inflammation and dyslipidemia. Based on recent NHANES data, 23.5%

of normal-weight US adults are metabolically abnormal, whereas 51.3% of overweight adults and 31.7% of obese adults are metabolically healthy (7). High Inhibitors,research,lifescience,medical circulating levels of insulin may prevail in both normal weight and obese individuals and in turn, as depicted by Chen and colleagues (6), insulin may be pro-tumorigenic either directly via the insulin receptor and insulin-like growth factor I receptor (IGF-IR), or indirectly through changes in the IGF-binding Inhibitors,research,lifescience,medical protein balance favoring Alvocidib molecular weight IGF-IR activation. When one takes

these into consideration, it is Inhibitors,research,lifescience,medical perhaps not surprising that BMI and other anthropometric surrogates may not be ideal predictors of cancer treatment and outcome. Further complexity is gleamed by the recent recognition that the metabolically abnormal status of an individual is more below strongly driven by fatty liver changes (non-alcoholic steatohepatitis, NASH) rather than by, as conventionally believed, visceral (central) fat (8). Fig 1. Serum insulin levels increase with increasing BMI. Results for fasting samples. Combinational oxaliplatin is now widely used in the treatment of metastatic colorectal cancer, and in many cases, the metastatic disease occurs in the liver. Initial responses are good (greater than 50%) but the development of chemoresistance is almost inevitable. Pulling together the various new insights into insulin resistance and the importance of fat distribution in the liver, the clinical importance of the ‘insulin milieu’ and chemotherapy becomes clearer.

Additional sections should include proximal and distal margins, radial margin (if not included in tumor sections), any additional polyps or lesions, and random uninvolved colorectum. After taking the above sections, the mesenteric fat or pericolorectal soft tissue is stripped off and dissected for lymph nodes. All grossly negative lymph nodes are entirely www.selleckchem.com/products/i-bet151-gsk1210151a.html submitted for microscopic examination. Inhibitors,research,lifescience,medical Grossly positive lymph

nodes may be submitted in part or entirely depending on their size. A polypectomy specimen is inked at the cauterized base, but the stalk may retract and thus be difficult to identify. The specimen is either bisected or serially sectioned depending on its size, and entirely submitted. Sectioning should follow the vertical plane of the stalk to maximize the histologic evaluation of polypectomy margin and submucosal Inhibitors,research,lifescience,medical involvement. If the specimen is received in multiple

pieces, however, margin evaluation may become impossible. Precursor lesions It has been well established that the vast majority of colorectal adenocarcinomas derive from precursor lesions such as adenomas and dysplasia. Residual adenoma is a common Inhibitors,research,lifescience,medical finding in colorectal adenocarcinomas. Endoscopic polypectomy decreases the incidence of colorectal cancers in treated population and prevents death from colorectal cancer (35,36). Some of the common precursor lesions are discussed here. Adenomas At least half of adults in Western

countries will have an adenomatous polyp in their lifetime and one-tenth of these lesions will progress to adenocarcinoma Inhibitors,research,lifescience,medical (37). The risk increases after the age of 50. Endoscopically, adenomas can be pedunculated or sessile. By definition, adenomas are clonal lesions that show at least low grade dysplasia characterized by enlarged, hyperchromatic and elongated (pencillate) nuclei Inhibitors,research,lifescience,medical arranged in a stratified configuration along the basement membrane. The adenomatous cells may show mucin depletion and increased apoptotic activity. Interestingly, adenomatous polyps appear to develop through a “top-down” mechanism (38). As such, small lesions will often only have adenomatous epithelium in their superficial portions. Conventional next adenomas are subclassified as tubular, tubulovillous and villous based on their architectural features (Figure 9). Tubular adenomas are composed of simple crypt-like dysplastic glands and contain <25% villous component. Villous adenomas consist of >75% villous component that resemble finger-like projections. Tubulovillous adenomas are intermediate lesions with 25-75% villous component. Adenomas that are large in size (>1 cm) or predominantly villous, or contain high grade dysplasia (discussed below) are considered “advanced adenomas” (39), which require more aggressive endoscopic surveillance. Figure 9 Examples of tubular adenoma (A.

linkage studies require recruitment, of family units of varying size, and are not, practically feasible in the context, of pharmacogenetics. Family-based association studies require smaller family units, but they too are not practical for pharmacogenetics, except, for studies conducted in pediatric populations. Case-control association studies are the most suitable strategy for pharmacogenetics. Their advantages

are considerable, the most, striking being the possibility of recruiting Inhibitors,research,lifescience,medical large samples that have sufficient, statistical power to investigate genetic variants of relatively small effect. Large samples are particularly important if the effect of more than one gene is being Inhibitors,research,lifescience,medical studied in the same sample, and interactions among genes and between genes and the environment, are being sought. On the other hand, case -control designs are notoriously susceptible to the effects of ethnic stratification, which can lead to spurious results. These are due to a BIBR 1532 supplier particular allele being enriched in a particular population. If this population is overrepresented in the case or control group, a spurious finding will result, in which the allele is erroneously associated with the phenotype. The nature of the problem is illustrated in Figure 1,6 which shows the frequency of the gly allele Inhibitors,research,lifescience,medical of the dopamine D3 receptor gene (DRD3) scr9gly polymorphism

in samples from several populations. These samples were included in a pooled and meta-analytic study of the DRD3 ser9gly polymorphism as a risk factor for TD.6 Great variability in the frequency of the 9gly allele in the different samples included in the study Inhibitors,research,lifescience,medical is immediately evident, ranging from 30% to 40% among Caucasians from different countries, and reaching 80% among African-Americans. Figure 1. Frequency of the gly allele of the dopamine D3 receptor (DRD3) ser9gly polymorphism in eight samples of different ethnic origin, vhich were included

in a pooled Inhibitors,research,lifescience,medical meta-analysis in which association of the DRD3 ser9gly polymorphism with susceptibility to … If the association of the DRD3 gly 9 allele with TD Terminal deoxynucleotidyl transferase were tested without controlling for ethnicity in this pooled sample, made up of 317 patients with TD and 463 patients without TD, spurious results could easily arise. Therefore, a stepwise logistic regression was employed so as to allow the confounding effects of ethnicity and also age and gender to be taken into account. TD was significantly associated with DRD3 gly9 allele carrier status (X2=4.46, df=1, P=0.04) over and above the effect, of ethnicity. Similar positive effects were observed when controlling for age and gender (X2=5.02, df=1, P=0.02).6-9 A meta-analysis was performed, which included all the samples in the pooled analysis, as well as data from additional published studies.

On the other hand, an age-related decline in inhibitory processes reflected by a decreased P2 component has been shown (Lister et al. 2011). Our findings argue against such an interpretation: YA showed a stronger P2 amplitude in the speech task versus the nonspeech task (i.e., in the task that requires less inhibition because no distractors have to be suppressed), whereas OA showed no modulation of the P2 component at all. Moreover, the topographic distributions of

both AEP amplitudes at Inhibitors,research,lifescience,medical issue were comparable in both age groups. A shift into frontal regions, which is a typical indicator of inhibitory processes, was not observed in our study (see Fig. 3). Two alternative explanations may account for the lack of any task-related modulation of the P2 component in OA. First, it could mean that the results are in line with the findings in YA, suggesting that P2 does not represent see more neural inhibition. Second, one may assume that an age-related decrease in the inhibition processes in older participants is already Inhibitors,research,lifescience,medical apparent in the AEP, but that this degeneration process is yet

not implied by behavioral output. To flesh out these possibilities, a longitudinal assessment is necessary. Are N1 and P2 two independent substeps of sensory Inhibitors,research,lifescience,medical processing? YA and OA showed similar task accuracy, but demonstrated substantial differences in age-related neurophysiological response pattern. Because N1 and P2 seem to be originated from (according to the topographical maps) distinct neural generators and processing steps, it can be assumed that the occurrence of both the N1 and P2 component is not an essential requirement for accomplishing the task. Inhibitors,research,lifescience,medical In our view, two possible interpretations can

be provided. The lack of an additional P2 task-related modulation in OA represents either: An increased efficiency in processing speech stimuli. This, due to a longer exposure to language and speech that is also substantiated by an enhanced mental lexicon as measured with the behavioral MWT-B. Or The consequence of an unspecific Inhibitors,research,lifescience,medical age-related neural degeneration process. In our opinion the latter argument seems more plausible because our stimulus material consisted of very frequent words. Its processing does not require a profound linguistic expertise. The most important finding, however, of this study pertains to Org 27569 an inconsistency between behavioral and neurophysiological data. In particular, while we observed age-related differences in the neurophysiological pattern we did not find corresponding effects in the behavioral task accuracy (i.e., discrimination between words and pseudowords, or between short and long white noise stimuli, respectively). Therefore, our findings indicate that the significantly different neural response patterns in younger and older participants were apparently not caused by an inability to understand or perform the tasks per se.

Another detection method is DNA sequencing, which can detect all possible mutations in the KRAS gene, not just limited to codons 12 and 13. In comparison to the traditional Sanger sequencing

method, the pyrosequencing technology offers a higher analytical sensitivity and is more advantageous for the analysis of DNA samples extracted from paraffin-embedded tissue blocks (130,131). BRAF testing In addition to KRAS, mutations in other members of the EGFR signaling pathway can also cause resistance to anti-EGFR therapy. A good example is BRAF (v-raf murine sarcoma viral oncogene homolog B1) gene Inhibitors,research,lifescience,medical mutation, which has been reported in ~10% of colorectal cancers (132-134). There are SRT1720 clinical trial several interesting facts about BRAF mutation in colorectal cancers. First, activating BRAF and KRAS mutations are almost always mutually exclusive (135,136), and thus mutation testing of the BRAF gene Inhibitors,research,lifescience,medical should be considered following a negative KRAS mutation analysis. In fact, many laboratories offer reflex BRAF test if no KRAS mutation is detected in a specimen. Second, almost all BRAF mutations are identical V600E point mutation (134), which can be readily detected by a number of commercially

available PCR-based assays (137). Third, BRAF mutation is almost exclusively seen in sporadic MSI tumors that are presumed to develop through the serrated tumorigenic pathway, but Inhibitors,research,lifescience,medical has never been reported in Lynch syndrome (138). More specifically, activating mutation of the BRAF gene is associated with a high level of global DNA methylation and epigenetic silencing of the MLH1 gene, found in 70-90% of sporadic colorectal tumors with a microsatellite unstable phenotype (136,139). Inhibitors,research,lifescience,medical Therefore, further testing BRAF mutation in a MSI tumor will help clarify the sporadic Inhibitors,research,lifescience,medical or syndromic nature of the tumor (140). Fourth, the impact of BRAF mutation on prognosis appears MSI-dependent. As expected, BRAF wild-type MSI-H tumors have the best prognosis, whereas BRAF-mutated MSS tumors are associated with the worst

outcome. BRAF-mutated MSI-H tumor and BRAF wild-type MSS old tumor are intermediate in terms of prognosis (132,133). Therefore, testing for both MMR abnormalities and BRAF mutations offers additional prognostic information. Conclusions Colorectal adenocarcinoma is a heterogeneous disease that involves multiple tumorigenic pathways. Pathologic analysis provides histologic and molecular information critical to appropriate patient treatment, prognosis assessment, and family counseling. Further understanding the molecular mechanisms in tumorigenesis will certainly lead to the development of new targeted therapies and new molecular tests, which will ultimately benefit the patients and their families. Acknowledgements Disclosure: The authors declare no conflict of interest.

The main advantage of cytometry over immunohistochemical analysis in the initial diagnosis is speed, and may be helpful when the material for immunohistochemical analysis is not available, such as in the case of fine-needle aspiration (9). ALCL is a T-cell lymphoma immunophenotypically characterized by positive CD30 staining in a membranous and Golgi zone pattern. Ganetespib supplier Approximately 60-85% ALCL cases are Inhibitors,research,lifescience,medical positive for ALK protein. The translocation

[2;5] between the ALK gene on chromosome 5 is the most common cytogenetic abnormality that leads to upregulation of ALK protein. The majority of ALC cases will show one or more

T-cell-associated antigens. However, there are cases of ALCL that are negative for all T-cell markers and they are known as null-cell type. The optimal treatment is not yet defined due to the low incidence of this disease. Surgery, radiotherapy and chemotherapy were all reported Inhibitors,research,lifescience,medical as treatment modalities alone or in combination Inhibitors,research,lifescience,medical (11). Only 17 patients, including our case, have been surgically treated. The importance of surgical resection for a cure or for a reduction of tumor burden cannot be assessed by this limited series. Whether or not systemic treatment with chemotherapy will give comparable results Inhibitors,research,lifescience,medical to surgery in resectable cases is also not currently known. Pescovitz et al. (10) noted that the disease-free survival rate for 5 patients

treated with resection and combined chemotherapy was 80%, compared with 54% survival for chemotherapy alone. But Page et al. (7) reported complete remission in 83.3% of 24 cases evaluated with combination chemotherapy. Five year cause specific and failure free survival rates were 87.1% and 70.1% respectively. Outcomes are poorer in patients with AIDS, and in those with coexisting liver disease. Currently, the most common Inhibitors,research,lifescience,medical treatment of PHL involves combination chemotherapy CHOP. Rituximab, an anti CD 20 monoclonal antibody, is added to this chemotherapy regimen if the histology confirms that the lymphoma PAK6 is CD 20 antigen positive. Massive liver infiltration, high index of proliferation, advanced age, elevated LDH levels, cirrhosis and increased levels of β2-microglobulin are the worst prognosis factors (12). This is, to our knowledge, the first reported case of primary hepatic anaplastic large cell Ki-1 non-hodgkin lymphoma in a setting of adult celiac disease. The only link between both diseases is a markedly increased incidence of gastrointestinal T-cell lymphoma in celiac disease.

The fungicidal/fungistatic natures of the extracts were determined as described by Thompson.9 The inhibited fungal discs from the extract treated dishes were sub-cultured in a fresh medium, and revival of their growth indicated fungistatic effect, while absence of any growth indicated fungicidal effect. Experimental Animals In this study, 72 Swiss albino mice (36 males and 36 females; 7–8 weeks old; 20–) and 50 Wistar albino

rats (25 males and 25 females; Inhibitors,research,lifescience,medical 6–8 weeks old; 120–) were used. They were bred in the animal house of the Department of Biochemistry, University of Dschang, Cameroon. The animals were housed two or three per cage in elevated wire mesh cages, and were provided with standard animal food, grower’s mash (Grand Cereals LTD, Jos-Nigeria) and water ad libitum. Acute Toxicity Study This study Inhibitors,research,lifescience,medical was carried out on Swiss albino mice (males and females) as described by Emerson and co-workers.10 A total of 72 mice, 6-8 weeks old were used. The mice of each sex were divided

into 6 subgroups of 6 animals each. Stock solution of crude extract (0.8 g/ml) was prepared using 1% aqueous solution of DMSO. Mice in subgroup 1 (control) Inhibitors,research,lifescience,medical were given (oral gavage) 1% aqueous solution of DMSO (1 ml per BW) while those of subgroups 2, 3, 4, 5 and 6 were administrated 2, 8, 16, 24

and 28 g/kg BW of crude extract, respectively. All the animals were fasted for 18 hours prior to the extract administration. After a single dose administration, Inhibitors,research,lifescience,medical the animals were observed for the first 3 hours for behavioral changes.11 Deaths were counted Inhibitors,research,lifescience,medical for the first 48 hours. The survived mice were closely observed for two weeks, and were monitored daily for behavioral changes, signs of toxicity and the latency of death. The median lethal dose (LD50) was determined by calculation.12 XAV-939 in vitro Sub-Acute Toxicity Study Fifty Wistar albino rats (25 males and 25 females) were used. Animals of each sex were divided into 5 subgroups of 5 animals each. They were kept under the same conditions as described above. about Rats in subgroup 1 (control) were given daily administration of 1% DMSO (1.5 ml per BW) by oral gavage, while those of subgroups 2, 3, 4 and 5 were given 25, 50, 100 and 200 mg/kg BW of the crude extract, respectively for four weeks. All animals were provided with food and water ad libitum. They were then observed for physiological and behavioral changes. Body Weight Trend The body weight of each rat was determined during the acclimatization period, once before the commencement of vehicle or extract administration, once every day during the administration period, and once on the day of the sacrifice.