Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.
We present a brief description of a valence-universal multireference coupled cluster (VU-MRCC) theory that can handle completely general incomplete model spaces, remaining close to the intermediate normalization (IN) condition for omega as much as possible without violating extensivity and without the use of a post facto correction. In this formalism, the connectedness of the cluster operators as well as effective Hamiltonian and hence the extensivity of the corresponding roots is achieved by invoking appropriate decoupling conditions on the special type of wave operator omega = {exp(S + X(cl))} satisfying the Bloch equations in the Fock-space S in an excitation operator and X is a closed operator (denoted by cl). This special type of wave-operator leads to a unique partition of the excitations from the model space into those generated by the cluster operators (open and quasi-open) and those generated by the effective Hamiltonian (closed). In this formulation, for every X(cl), there is a counterterm from {exp(S)}(cl) canceling each other. This leads to a connected expressions for cluster amplitudes, using the constraint omega(cl) = 1. The new form of the effective Hamiltonian preserves the extensivity of the target energies. Our analysis implies that IN for omega is a valid size-extensive normalization for certain special IMS such as the quasi-complete model space and the isolated incomplete model space.
The time-dependent dissociation probabilities, lineshapes of dissociation rates and branching ratios of photofragments between the neutral hydrogen and deuterium channels have been investigated for resonant two-photon dissociation of HD+ from the ground level in the presence of two laser fields of different intensities I1, I2 and frequencies omega 1, omega 2 using the resolvent operator formalism. The symmetry breaking due to non-adiabatic (NA) interactions causes splitting between the two asymptotic channels, unlike the Born-Oppenheimer (BO) approximation. Simultaneous dissociation to the continua of the two electronic states at two different energies occurs through the absorption of either omega 1+ omega 2 or 2 omega 1 photons. Only the field of frequency omega 1 was considered to resonantly couple the near-resonant level nu '=17, J'=1 or nu '=18, J'=1 to the ground level nu =0, J=0. Non-resonant discrete and continuum states significantly affect the dissociation process in the case of high intensity fields. The electric field gauge (E.d) form of interaction Hamiltonian has been used in the computation of various laser-dependent parameters. The results with NA coupling included are found to deviate appreciably from those obtained with the BO approximation.
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