Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.

PURPOSE: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. EXPERIMENTAL DESIGN: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. RESULTS: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as with a none. CONCLUSION: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.     

Prevalence of HBV infection among the healthy Nepalese males: a serological survey

Sera from 478 healthy Nepalese male population, inhabiting various districts of five development regions of Nepal were collected from October 1996 to March 1997 and examined for the presence of HBsAg by third generation ELISA and Latex agglutination test in the laboratory of Central Department of Microbiology, Tribhuvan University, Kirtipur. The surface antigen was detected by ELISA in 4.0% (19/478) of subjects studied. However, different results were obtained in Latex agglutination test. The correlation between the results obtained from these two different tests is statistically significant (chi2=85.11, P<0.05). The results obtained from ELISA showed the probability of Nepal to fall in WHO category of intermediate endemicity zone for hepatitis B infection. The percent positivity of HBsAg was found to increase steadily from Eastern (2%) to Far Western (6.2%) development regions. Among the districts studied, Kailali district gave characteristically high prevalence followed by Rukum and Kaski. Other, districts representing for the prevalence are Sankhuwasabha, Jhapa, Ramechhap, Sarlahi, Dhanusa, Baglung, Gulmi, Palpa and Dang. None of the samples represented from Kathmandu valley were positive for HBsAg. The age groups of 16-20 years and 36-40 years were found to be associated with the hepatitis B infection. Furthermore, various percent prevalence of the infection were encountered from 16 to 40 years subjects and a single case was also observed from 63 years old man. All the samples recorded positive for HBsAg from ELISA were assayed for the amount of ALT as a liver function test. Where, 15.8% (3/19) of the infected subjects had impaired liver function, hence it showed that, the subjects with high ALT to be the possible carrier of the HBV. Conversely, the remaining 84.2% (16/19) of the total HBsAg positive subjects were concluded to have the infection either at incubation or at prodrome period.     

The vulpius procedure for correction of equinus deformity in patients with hemiplegia

Spasm or contracture of gastrocnemius causes an equinus deformity of the ankle in both cerebral palsy and hemiplegia. Its release is therefore required in the treatment of those patients who do not respond to conservative measures. The Vulpius procedure is a simple and effective method for the release of gastrocnemius and is particularly indicated when long periods of immobilisation of the foot and ankle are not desirable. We have used this procedure with good results to correct an equinus deformity in 230 adults with a cerebrovascular accident and various associated medical conditions. It is not only effective in cerebral palsy, but should be considered at an early stage in all adult patients with deformity of the ankle and foot in whom spasm of gastrocnemius is the major cause.     

Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin c-terminal alpha-helical segment

Mutations in desmin gene have been identified in patients with cardiac and skeletal myopathy characterized by intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates. We characterized two new desminopathy families with unusual features of adult-onset, slowly progressive, diffuse skeletal myopathy and respiratory insufficiency. Progressive reduction of respiratory muscle strength became clinically detectable between the 3rd and the 8th years of illness and led to recurrent chest infections and death in one of the patients. Novel mutations, A357P and L370P, predicted to introduce proline residue into a highly conserved alpha-helical region of desmin, were identified. Proline is known to disrupt the alpha-helix. In addition, the A357P mutation distorts a unique stutter sequence that is considered to be critically important for proper filament assembly. Functional assessment in two cell-lines, one of which does and the other of which does not constitutively produce type III intermediate filaments, demonstrated the inability of mutant desmin carrying either the A357P or the L370P mutation to polymerize and form an intracellular filamentous network. The results of this study indicate that respiratory insufficiency is an intrinsic feature of disease associated with specific desmin mutations; in some patients, respiratory weakness may present as a dominant clinical manifestation and a major cause of disability and death.     

Livedo reticularis associated with the use of a midline catheter

We report a case of livedo reticularis as an unusual complication of a midline catheter in a patient being treated for pyelonephritis with intravenous antibiotics. The rash resolved completely after catheter removal. The constellation of symptoms suggested an aberrant autonomic response as the cause of the illness.     

Liver transplantation for acute liver failure from drug induced liver injury in the United States.

Studies of acute liver failure from drugs have included cases mostly attributed to acetaminophen (APAP) but have reported limited data on other drugs. We used the United Network for Organ Sharing (UNOS) liver transplant database from 1990 to 2002 to identify recipients and estimate a U.S. population-based rate of liver transplantation due to acute liver failure from drugs. Patients were identified if their diagnosis was acute hepatic necrosis from an implicated drug at the time of transplant. Liver transplantation for drug hepatotoxicity accounted for 15% of liver transplants for acute liver failure over the study period. In our cohort (n = 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the non-acetaminophen (non-APAP) group (n = 137), the most frequently implicated drugs were: isoniazid, n = 24 (17.5%); propylthiouracil, n = 13 (9.5%); and phenytoin and valproate in 10 (7.3%) cases each. One-year patient and graft survival for the entire cohort was 77 and 71%, respectively. Among Caucasians (n = 206) and African-Americans (n = 48), APAP only was implicated in 110 (53%) patients and 12 (25%) patients, respectively, and non-APAP drugs were implicated in 96 (47%) patients and 36 (75%) patients, respectively (P =.0004). Among African-Americans in the non-APAP group, 28 (78%) were women. In conclusion four drugs were implicated in 42% of patients undergoing liver transplantation for acute liver failure due to drugs other than APAP. The increased frequency of African-American women undergoing liver transplantation for non-APAP drug induced liver injury warrants further study.     

Recovery from impaired dark adaptation in nightblind pregnant Nepali women who receive small daily doses of vitamin A as amaranth leaves, carrots, goat liver, vitamin A-fortified rice, or retinyl palmitate

BACKGROUND: It is not known whether daily consumption of vitamin A-containing foods is efficacious for treating nightblindness. OBJECTIVE: We assessed the effect of supplementation with vitamin A from food or synthetic sources on dark adaptation and plasma retinol concentrations in nightblind pregnant Nepali women. DESIGN: Nightblind pregnant women were randomly assigned to 1 of 6 treatment groups to receive 6 d/wk for 6 wk either 850 microg retinol equivalents/d as retinyl palmitate, vitamin A-fortified rice, goat liver, amaranth leaves, or carrots or 2000 microg retinol equivalents/d as retinyl palmitate. Dark adaptation was assessed weekly by using the pupillary threshold (PT) test; plasma retinol concentrations were measured before and after the intervention. These outcomes were also assessed in a comparison group of nonnightblind pregnant women. RESULTS: In the nightblind women, the mean PT improved significantly (P<0.0001) from -0.71+/-0.04 to -1.42+/-0.02 log cd/m2, and the final mean PT did not differ significantly from that in the nonnightblind women (-1.43+/-0.04; P=0.55). Improvement in dark adaptation was greater in the liver group than in the vitamin A-fortified rice group (P<0.02). Plasma retinol concentrations increased significantly (P<0.0001) from 0.95+/-0.05 to 1.07+/-0.05 micromol/L. The plasma retinol response was greater in the higher-dose capsule and liver groups than in the vegetable groups and significantly greater in the liver group than in the vitamin A-fortified rice group (both: P<0.05). CONCLUSION: Improvement in dark adaptation did not differ significantly between women who received vitamin A as liver, amaranth leaves, carrots, or retinyl palmitate.