Radioprotective effect of podophyllotoxin in Saccharomyces cerevisiae.

Recent reports showed that whole extract of Podophyllum hexandrum was radioprotective in mice. Podophyllotoxin is one of the major constituents of the whole extract of Podophyllum. In this study we report on the radioprotective action of podophyllotoxin in Saccharomyces cerevisiae yeast. Proliferating yeast cells pretreated with podophyllotoxin (2.5-5.0 microg/mL) for > or =3 hours showed a higher surviving fraction after (60)Co-gamma-irradiation (200-600 Gy) than did the irradiated cells not pretreated with podophyllotoxin. The maximum increase (2.0 times) in surviving fraction was observed in cells treated with 2.5 microg/mL podophyllotoxin, 5 hours before (60)Co-gamma-irradiation (400 Gy). Podophyllotoxin was not mutagenic or recombinogenic at radioprotective doses (2.5 microg/mL). A post-irradiation decrease in revertants and gene convertants was observed in cells treated with podophyllotoxin (2.5 microg/mL podophyllotoxin, -5 hours, 400 Gy). This study indicates that podophyllotoxin is radioprotective in yeast, and its radioprotective effects in higher eukaryotes would be worth investigating.     

Epilepsy in Ancient India

The ancient Indian medical system, Ayurveda, meaning science of life, is the oldest system of medicine in the world. Epilepsy is defined as Apasmara: apa, meaning negation or loss of; smara, meaning recollection or consciousness. Aura was recognized and was called Apasmara Poorva Roopa. A large number of symptoms indicative of aura were listed. Worthy of mention are subjective sensation of sounds, sensation of darkness, feeling of delusion, and dream-like state. An actual attack of Apasmara includes falling down; shaking of the hands, legs, and body; rolling up of the eyes; grinding of the teeth; and foaming at the mouth. Four major types of epilepsy based on the disturbance of doshas (humors) that govern the physiological and physiochemical activities of the body are mentioned. Apasmara is considered a dangerous disease that is chronic and difficult to treat. Several causes are mentioned. Treatment included correcting the etiological factors and dietary regimen and avoiding dangerous places that may result in injuries.     

Subacute (acute,persistent) thrombotic microangiopathy

Six patients with prolonged acute courses of thrombotic microangiopathy are reviewed. These patients had in common courses of acute disease requiring plasma support for more than 3 months, with subsequent complete remission. Plasma support requirements may be prodigious, and the acute course may require more than 100 plasma exchanges before a stable remission is achieved. These patients appear to represent a subset of thrombotic microangiopathy distinct from the more common acute T.T.P. course, which resolves in 3–6 weeks, and the chronic relapsing pattern, which may have a short or prolonged acute course. © 1992 Wiley-Liss, Inc.     

p-Amino salicylic acid — oxidized cellulose system: a model for long term drug delivery

The immobilization of p-amino salicylic acid (PASA) on periodic oxidized cellulose (O.C) as a biocompatible carrier was investigated. The immobilization of the PASA is based on Schiff's base formation between the amino group of PASA and the aldehyde group of O.C. The in vivo and in vitro release of p-amino salicylic acid was studied. Such a system may be useful for the sustained delivery of the drugs in the body, since O.C. itself is a biosoluble carrier.     

Selective transport of an oligomeric IgA into canine saliva

Evidence is presented which shows that an oligomeric IgA myeloma protein possessing J-chain but lacking secretory component, is selectively transferred from serum into canine saliva. The data also demonstrate that 125I-label remains with the IgA during the transfer process. These data interpreted in the light of findings in humans support the concept that the oligomeric form of IgA, devoid of secretory component, is required to achieve selective transport.     

Polyamine content and drug sensitivities of different clonal lines ofLeishmania infantum promastigotes

Two isolates (skin and lymph node) ofLeishmania infantum obtained from a naturally infected dog were cloned and the free pools of polyamines for both complete isolates and clones were determined. Putrescine (Put) and spermidine (Spd) levels were highly variable among the lines studied, ranging from 0.89 to 2.1 nmol Spd/10⁷ promastigotes. The Put/Spd ratio was also variable (1.54–0.51) and correlated with the cell growth of the lines studied. There were important differences in the clones' sensitivites to difluoromethylornithine (DFMO) and Berenil, with some of the clones being almost refractory to the inhibitory effect of 50 M DFMO, whereas the growth of others was reduced by 60%; similar findings were obtained with 50 M Berenil.L. infantum sensitivites to DFMO and Berenil were correlated and apparently related to the values for the Put/Spd index.     

Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity

Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease.     

The role of mineralization and organic matrix in the microhardness of bone tissue from controls and osteoporotic patients

Degree of mineralization of bone (DMB) is a major intrinsic determinant of bone strength at the tissue level but its contribution to the microhardness (Vickers indentation) at the intermediary level of organization of bone tissue, i.e., Bone Structural Units (BSUs), has never been assessed. The purpose of this study was to analyze the relationship between the microhardness, the DMB and the organic matrix, measured in BSUs from human iliac bone biopsies. Iliac bone samples from controls and osteoporotic patients (men and women), embedded in methyl methacrylate, were used. Using a Vickers indenter, microhardness (kg/mm2) was measured, either globally on surfaced blocks or focally on 100 microm-thick sections from bone samples (load of 25 g applied during 10 sec; CV=5%). The Vickers indenter was more suited than the Knoop indenter for a tissue like bone in which components are diversely oriented. Quantitative microradiography performed on 100 microm-thick sections, allowed measurement of parameters reflecting the DMB (g/cm3). Assessed on the whole bone sample, both microhardness and DMB were significantly lower (-10% and -7%, respectively) in osteoporotic patients versus controls (p<0.001). When measured separately at the BSU level, there were significant positive correlations between microhardness and DMB in controls (r2=0.36, p<0.0001) and osteoporotic patients (r2=0.43, p<0.0001). Mineralization is an important determinant of the microhardness, but did not explain all of its variance. To highlight the role of the organic matrix in bone quality, microhardness of both osteoid and adjacent calcified matrix were measured in iliac samples from subjects with osteomalacia. Microhardness of organic matrix is 3-fold lower than the microhardness of calcified tissue. In human calcanei, microhardness was significantly correlated with DMB (r2=0.33, p=0.02) and apparent Young's modulus (r2=0.26, p=0.03). In conclusion, bone microhardness measured by Vickers indentation is an interesting methodology for the evaluation of bone strength and its determinants at the BSU level. Bone microhardness is linked to Young's modulus of bone and is strongly correlated to mineralization, but the organic matrix accounts for about one third of its variance.