Origins of Incomplete Fusion Products and the Suppression of Complete Fusion in Reactions of

Above-barrier complete fusion involving nuclides with low binding energy is typically suppressed by 30%. The mechanism that causes this suppression, and produces the associated incomplete fusion products, is controversial. We have developed a new experimental approach to investigate the mechanisms that produce incomplete fusion products, combining singles and coincidence measurements of light fragments and heavy residues in ^{7}Li+^{209}Bi reactions. For polonium isotopes, the dominant incomplete fusion product, only a small fraction can be explained by projectile breakup followed by capture: the dominant mechanism is triton cluster transfer. Suppression of complete fusion is therefore primarily a consequence of clustering in weakly bound nuclei rather than their breakup prior to reaching the fusion barrier. This implies that suppression of complete fusion will occur in reactions of nuclides where strong clustering is present.

Mechanisms Suppressing Superheavy Element Yields in Cold Fusion Reactions.

Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.

Sarcoptic mange in wombats-A review and future research directions.

Sarcoptic mange is caused by the mite Sarcoptes scabiei and has recently been recognized as an emerging infectious disease of wildlife worldwide. The mite is one of the main causes of population decline in southern hairy-nosed (Lasiorhinus latifrons) and bare-nosed wombats (Vombatus ursinus). This review focuses on Sarcoptes scabiei infestations in wombats and provides insights into why the disease may be so prevalent in wombats. Current treatment practices and trials conducted in the field to reduce the incidence of sarcoptic mange in wombats are described and critically reviewed. Current and potential future avenues of research are discussed.

National seroprevalence of Toxoplasma gondii in India.

This article reports the first national serological prevalence of Toxoplasma gondii in India. In total, 23,094 serum samples were tested for T. gondii IgG and IgM antibodies with the use of a solid-phase immunocapture ELISA. Antibodies (IgG) were found in 24.3%; IgM antibodies were detected in 2% of the samples. The lowest seroprevalences were in the northern parts of India, with the highest in the south. These data probably reflect the effects of significantly drier conditions and, therefore, a negative impact on the survivability of T. gondii oocysts.

Synthesis, glycosylation and rapid secretion of a glycoprotein by Achlya, a primitive eucaryote.

Achlya ambisexualis, a water mold, secretes several glycoproteins during exponential growth. Among these is a major protein of 39 000 daltons (protein A-39) which is secreted very rapidly. Protein A-39 is detected among the soluble cellular proteins labeled for 5 min. However, after longer labeling times, an additional 95 000 dalton glycoprotein was immunoprecipitated from among the cytoplasmic proteins by antiserum against protein A-39. This antiserum reacted with a single 37 000 dalton protein from the in vitro translation products of poly(A)-containing RNA in a wheat germ cell-free system which is cleaved to a faster moving component in the presence of dog pancreatic membranes. Immunoprecipitated, chain-completion products of polysomes also show a 37 000 dalton peptide which does not bind to lectins, indicating absence of co-translational cleavage and glycosylation. Tunicamycin inhibits the appearance of the 95 000 dalton protein. Several immunoprecipitable proteins, including protein A-39, having sizes identical to the secretory proteins accumulate in the cytoplasm in the presence of this inhibitor. A short pulse with [3H]glucosamine followed by a chase showed that incorporation in protein A-39 increases while that in 95 000 dalton protein is decreasing. These results suggest that the 95 000 dalton glycoprotein may serve as a glycosyl donor to secretory protein A-39.

Antigenaemia and antibody response to Toxoplasma gondii in human immunodeficiency virus-infected patients.

Toxoplasma encephalitis in immunocompromised patients results from reactivation of previously acquired (latent) infection. The aim of the study is to assess the antigenaemia and antibody response to Toxoplasma gondii in human immunodeficiency virus (HIV)-infected patients to determine the best marker for early diagnosis of toxoplasmosis in such patients. Indirect enzyme-linked immunosorbent assay (ELISA) for detection of IgG, IgM and IgA anti-toxoplasma antibodies and double-sandwich ELISA for toxoplasma antigen is carried out in serum samples collected from 100 HIV seropositive patients and 75 controls. Toxoplasma-specific IgG, IgM and IgA antibody response and antigenaemia were detected in 12%, 6%, 7% and 14% of HIV-infected patients, respectively. On retrospective analysis of 14 patients with antigenaemia only one had central nervous system (CNS) symptoms attributable to toxoplasma infection. In this patient, the CD4+ cell count was below 50/microL and none of the specific immunoglobulin isotype responses could be detected. The patient showed clinical improvement following specific chemotherapy for toxoplasmosis. In 25 HIV-negative and anti-toxoplasma IgG antibody-positive controls, IgM was detected in two (8%), IgA in five (20%) and antigenaemia in 10 (40%), while 50 HIV seronegative healthy controls were negative for both antigen and antibody responses. The study indicates that detection of toxoplasma antigen in addition to IgG antibody response may prove to be a useful indicator in the early diagnosis of reactivated toxoplasmosis in HIV/AIDS patients.

Cysteine, a chelating moiety for synthesis of technetium-99m radiopharmaceuticals--Part IV. Benzyl cysteine and derivatives.

To explore the possibility of utilizing cysteine derivatives for technetium-99m radiopharmaceutical preparation with clinical potential, we synthesized two benzyl substituted cysteine compounds, namely, S-benzyl cysteine 1 and cysteine benzyl ester 3. It was expected, from our previous studies on benzoyl cysteines, that the above two ligands after chelation with 99mTc would be excreted by the hepatobiliary pathway. Although for 99mTc-3 the above expectation was realized, 99mTc-1 behaved in a most unexpected way by affixing itself with kidney and selecting the renal tubular secretory pathway for its excretion. It is anticipated that the affinity of 99mTc-1 for kidney is due to its interaction with the kidney sulphhydryl group and it also formed an adduct with other sulphydryl containing compounds like thiophenol. In terms of the kidney-to-background ratio, 99mTc-1 showed some superiority over other kidney structure agents, like 99mTc-dimercaptosuccinic acid and 99mTc-glucoheptanoic acid and, therefore, the chelate (99mTc-1) may have the potential to replace the above two radiopharmaceuticals in clinical use.

Antigenaemia and antibody response to Leishmania donovani stage-specific antigens and rk39 antigen in human immunodeficiency virus-infected patients.

In order to define the possible markers for the early diagnosis of asymptomatic visceral leishmaniasis in human immunodeficiency virus (HIV)-infected individuals, the antigenaemia and antibody response to stage-specific Leishmania donovani and rk39 antigens is assessed by enzyme-linked immunosorbent assay (ELISA) and immunoreactivity to stage-specific antigens analysed by Western blot. Serum samples from two out of 100 HIV-infected individuals were found positive for antigenaemia, antibody response to stage-specific L. donovani antigens and rk39 antigen, and one sample was also positive for antigenaemia and antibody response to L. donovani antigens, while antibody detection to rk39 antigen was not carried on this sample. Additionally, one sample was found positive for amastigote antigenaemia and antibody response to amastigote antigen, while in this patient promastigote antigenaemia and antibody response to promastigote L. donovani and rk39 antigen could not be detected. One sample was found positive for antigenaemia, antibody response to amastigote antigen and negative for antibody response to promastigote antigen, while in this patient response to rk39 antigen was borderline. Although antibody response to rk39 antigen could be detected in 9/88 (10%) HIV-infected individuals, in six of these nine patients neither antigenaemia nor antibody response to stage-specific L. donovani antigens could be detected. All 10 confirmed visceral leishmaniasis and HIV-negative control patients had positive antigenaemia and antibody response to L. donovani amastigote and promastigote antigens, while all the normal healthy individuals were negative. The study indicated that detection of antibody response to rk39 antigen, amastigote antigenaemia and antibody response to amastigote antigen may prove to be better markers than detection of promastigote antigenaemia, antibody response to promastigote antigen and immunoblot reactivity.

Evaluation of glutathione and ascorbic acid as suppressors of drug-induced lipid peroxidation.

In different sets of experiment lipid peroxidation induction capacity of two drugs, viz., ceftizoxime sodium, a third generation cephalosporin antibiotic, and acyclovir, an antiviral agent, was studied using goat whole blood as the lipid source. Ceftizoxime sodium caused significant extent of lipid peroxidation. Lipid peroxidation being a toxicity mediating process, such observation may be related to the toxic potential of the drug. Insignificant induction of lipid peroxidation was found in case of acyclovir and this is in good agreement with the safety record of the drug. Glutathione and ascorbic acid could significantly reduce ceftizoxime sodium induced lipid peroxidation, suggesting that free radical scavenging action of antioxidants may be exploited by possible antioxidant co-therapy to reduce iatrogenicity of the drug in persons with impaired endogenous antioxidant defence. Glutathione and ascorbic acid appear to be promising candidates for further investigation in this regard.

Ethinyl estradiol: its interaction on blood-lipid.

Lipophilicity (log P) of the drug plays an important role when drug reaches in the critical reaction site, i.e., active site cum receptors where the major constituent is lipid moieties. The drug molecule may be responsible for altering the lipid constituents, which is measured in terms of phosphorus content and can be explained by their fatty acid changes that are linked with biological effect of the drug. Having considered the lipophilicity of ethinyl estradiol (log P = 3.67), its interactions with the whole lipid of goat blood have been investigated along with fatty acid changes and lipid peroxidation phenomena. There was significant loss of phosphorus content of phospholipid and change of fatty acid constituents of whole lipid. This may be ascribed to binding affinity of ethinyl estradiol with lipid constituents in blood. Lipid binding potential of the drug may have role in its therapeutic effect. The peroxidation induced by drug has been quantitatively measured along with its suppression by using antioxidant. The results reveal that ethinyl estradiol caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant could significantly reduce drug induced lipid peroxidation.

Effect of aspirin on blood-lipid interaction and lipid peroxidation phenomena in relation to partition coefficient and biological activity.

Considering the lipophilicity of aspirin (log P = -1.15), a significant contributor to its action mechanism, interaction of the drug with the whole lipids of goat blood have been investigated using phospholipid binding and lipid peroxidation phenomena as the parameters under investigation. The lipid content change along with the peroxidation induced by aspirin and its suppression with ascorbic acid had been quantitatively measured. Significant loss in phospholipid was observed after incubation of whole blood with aspirin in varying periods of time. This may be ascribed to binding affinity of aspirin with lipid constituents in blood, which may have potential role in its therapeutic effect. Lipid peroxidation induction potential of aspirin caused significant extent of peroxidation. Ascorbic acid, an antioxidant could significantly reduce aspirin induced lipid peroxidation.

Correlation of phospholipid loss in goat whole blood with solvochromic properties of antiamebics like emetine, metronidazole and diloxanide furoate.

Phospholipid content of whole blood lipid decreases significantly when goat blood is incubated for different length of time with different amebicidal agents (e.g., emetine, metronidazole and diloxanide furoate). The plots of relative per cent phosphate loss against incubation period show biphasic nature and suggest that the rates of phospholipid loss bears some relation with the drug's lipophilicity (log P in 1 octanol/water system). The absolute phospholipid loss seems to be governed by the drug's aquasolubility. Implication of these finding were discussed in terms of their clinical profiles assuming that the loss of phospholipid is due to drug's binding with the phospholipid layer in amebic cyst-coat, being the first step which may trigger a chain of events leading to the onset of drug action.

Effect of two cardiac glycosides, digitoxin and digoxin on blood lipids.

Two cardiac glycosides, namely digitoxin and digoxin when treated with goat blood, were found to alter the lipid constitution as measured by their phosphorus content, fatty acid composition and malonaldehyde content. There was significant increase in the poly-unsaturated fatty acids (PUFA) and malonaldehyde contents in blood treated with these drugs. Possible correlation between the lipophilicity of the drugs and their biological activity is discussed.

Effect of lignocaine on blood lipid in relation to partition coefficient and biological activity.

To correlate lipophilicity of lignocaine with changes in lipid composition of blood as a result of in vitro incubation with the drug, phosphorus content and fatty acid compositions of blood lipids before and after lignocaine treatment have been compared with those of a standard phospholipid, lecithin, under similar conditions of drug treatment. The change in fatty acid constituents has been correlated with the biological activity (both therapeutic and toxic) of lignocaine.

Effect of propranolol hydrochloride on blood cell lipids in relation to partition coefficient and biological activity.

Considering the high lipophilicity of propranolol (log P = 3.56), its interactions with the cell membrane lipids of goat blood have been investigated. It is observed that lipid loss after incubation of blood cells with propranolol hydrochloride in salt glucose medium for varying periods of time was accompanied with significant increases in PUFAs. Amongst the PUFAs studied the omega 3 and omega 6 fatty acids, the two important precursors of eicosenoids, have shown increase in varying amounts. This phenomenon is presumably responsible for the significant cardiovascular activity of this drug.

Effects of oral contraceptive norethindrone on blood-lipid and lipid peroxidation parameters.

Considering importance of the lipophilicity of norethindrone (log P=2.97), a significant contributor to its mechanism of action, interaction of the drug with total lipids of goat whole blood have been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation. The objective was to derive an insight into the pharmacodynamic behavior of the drug by correlating biological activity with drug induced changes in lipid constituents. Significant loss in phospholipid along with changes in fatty acid cotmposition was observed after incubation of whole blood with norethindrone at 56 ng/ml (effective contraceptive concentration in blood) in varying periods of time. This may be ascribed to binding affinity of norethindrone with lipid constituents in blood. Lipid binding potential of the drug may have a role in its therapeutic effect. Lipid peroxidation induction potential of norethindrone was quantitatively measured in the context of its toxicity. The results reveal that northindrone caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant, at equivalent human dose levels of 250 mg and 500 mg could significantly reduce norethindrone induced lipid peroxidation.

Ceftriaxone induced lipid peroxidation and its inhibition with various antioxidants: Part II. Evaluation of glutathione and probucol as antioxidants.

Exploratory studies on drug induced lipid peroxidation in goat whole blood and its inhibition with antioxidants were carried out using sodium ceftriaxone (CTS) as the representative drug and glutathione and probucol as the representative antioxidants. The studies showed that CTS could induce lipid peroxidation to a significant extent. Lipid peroxidation is a toxicity mediating process, this finding may be correlated with the toxic potential of the drug. It was further found that glutathione and probucol caused significant suppression of CTS induced lipid peroxidation. The results suggest that glutathione and probucol merit further assessment to explore their potential to reduce drug induced lipid peroxidation and thus to increase therapeutic index of the drug by way of reducing toxicity that may be mediated through free radical mechanism.

Exploring effects of different antioxidants on dexamethasone-induced lipid peroxidation using common laboratory markers.

As a part of our ongoing effort to explore drug-induced lipid peroxidation in relation to drug-induced toxicity, our recent observations on lipid peroxidation induction potential of dexamethasone, a commonly used glucocorticoid compound in inflammatory and allergic conditions, has been presented considering lipid peroxidation a possible mediator of toxicity. An attempt was made to see the suppressive actions of some conventional antioxidant compounds, viz, ascorbic acid, alpha-tocopherol and probucol on dexamethasone-induced lipid peroxidation. It was found from the study that dexamethasone increased malondialdehyde content vis-a-vas decreased the level of reduced glutathione significantly in the liver homogenate. This suggests that dexamethasone caused a significant extent of lipid peroxidation which may be related to the toxic potential of the drug. It was further found all of the above antioxidants could suppress dexamethasone-induced lipid peroxidation to the significant extent.

Evaluation of alpha-tocopherol, probucol and ascorbic acid as suppressors of digoxin induced lipid peroxidation.

Protective effects of three free radical scavengers, tocopherol (TOC), probucol (PR) and ascorbic acid (AA), on cardiotonic glycoside digoxin (DIG) induced lipid peroxidation in goat liver homogenate, have been studied by measuring malondialdehyde and glutathione contents as indicator parameters. The level of reduced glutathione decreased vis-a-vis malondialdehyde content increased in the drug treated samples in comparison with the controls. This suggests that DIG may have significant lipid peroxidation induction capacity. Considering lipid peroxidation as a toxicity mediating process, this may be related to the toxic potential of the drug. When the liver homogenate samples were incubated with antioxidant (TOC/PR/AA) in conjunction with the drug (DIG), lipid peroxidation was suppressed as indicated by increased level of reduced glutathione and decreased level of malondialdehyde in comparison with those of drug treated samples. This indicates that TOC, PR and AA may have considerable suppressive action on DIG induced lipid peroxidation. Thus, these antioxidants merit further extensive study to explore their potential in reducing DIG induced toxicity that may be mediated by free radical mediated process.