Alteration of the acute toxicity and various pharmacologic effects of streptomycin sulfate by calcium 4'-phosphopantothenate

The effect of calcium 4'-phosphopantothenate (CPP) on acute toxicity of streptomycin and the decrease by the antibiotic of the muscle working capacity, "holes" reflex, body temperature and oxygen intake was studied on 258 albino mice weighing 22-26 g. Medical calcium pantothenate (CPA) was used for control purposes. CPP is an antagonist of streptomycin sulfate. In a dose of 1/10 or 1/5 of the LD50 injected intraperitoneally CPP lowered acute toxicity of streptomycin and prevented its effect in a dose of 0.11--1.1 g/kg injected subcutaneously on the muscle working capacity, "holes" reflex and body temperature. The spectrum index of the CPP antitoxic effect was equal to 22.5. By its acute toxicity CPP (LD50 1.18 +/- 0.07 g/kg) did not differ from CPA (LD50 1.25 +/- 0.08 g/kg). The efficacy of CPP, by its antitoxic spectrum, was 1.8 times higher than that of CPA. CPA lowered the streptomycin effect on the "holes" reflex and body temperature, while CPP prevented it. Both the drugs did not influence the decrease in the oxygen consumption induced by streptomycin.     

Interaction of acetyl-CoA fragments with rat liver acetyl-CoA carboxylase

The interaction of acetyl-CoA fragments with rat liver acetyl-CoA carboxylase has been studied. Dephosphorylated acetyl-CoA did not actually differ from acetyl-CoA in its substrate properties. Non-nucleotide analogues of the substrate, S-acetylpantatheine and it's 4'-phosphate, also possess substrate properties (Vmax = 1.5% and 15% of the maximal rate value of acetyl-CoA carboxylation, respectively). The nucleotide fragment in the acetyl-CoA molecule produces a marked effect on the thermodynamics of the substrate-enzyme interaction, and is apparently involved in activation and appropriate orientation of the acetyl group in the active site. The better substrate properties of S-acetylpantetheine 4'-phosphate and the inhibitory properties of pantetheine 4'-phosphate, compared to the unphosphorylated analogues, evidence an important role of the 5'-beta-phosphate of 3'-phosphorylated ADP residue in acetyl-CoA binding to the enzyme.     

Coarse-grained molecular dynamics simulations of phase transitions in mixed lipid systems containing LPA, DOPA, and DOPE lipids

The mechanisms that mediate biomembrane shape transformations are of considerable interest in cell biology. Recent in vitro experiments show that the chemical transformation of minor membrane lipids can induce dramatic shape changes in biomembranes. Specifically, it was observed that the addition of DOPA to DOPE has no effect on the stability of the bilayer structure of the membrane. In contrast, the addition of LPA to DOPE stabilizes the bilayer phase of DOPE, increasing the temperature of a phase transition from the bilayer to the inverted hexagonal phase. This result suggests that the chemical conversion of DOPA to LPA is sufficient for triggering a dramatic change in the shape of biomembranes. The LPA/DOPA/DOPE mixture of lipids provides a simple model system for understanding the molecular events driving the shape change. In this work, we used coarse-grained molecular dynamics simulations to study the phase transitions of this lipid mixture. We show that despite the simplicity of the coarse-grained model, it reproduces the experimentally observed phase changes of: 1), pure LPA and DOPA with respect to changes in the concentration of cations; and 2), LPA/DOPE and DOPA/DOPE mixtures with respect to temperature. The good agreement between the model and experiments suggests that the computationally inexpensive coarse-grained approach can be used to infer macroscopic membrane properties. Furthermore, analysis of the shape of the lipid molecules demonstrates that the phase behavior of single-lipid systems is consistent with molecular packing theory. However, the phase stability of mixed lipid systems exhibits significant deviations from this theory, which suggests that the elastic energy of the lipids, neglected in the packing theory, plays an important role.     

Gene structure,transcripts and calciotropic effects of the PTH family of peptides in <Emphasis Type="Italic">Xenopus</Emphasis> and chicken

Background  

Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34) and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L) was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken.     

Unusual metastasis of papillary thyroid carcinoma to larynx and hypopharynx a case report

Background  

Although direct infiltration of papillary carcinoma of thyroid to larynx, trachea and esophagus is well recognized, lymphatic and vascular metastases to larynx and hypopharynx have rarely been reported.     

Vitamine-like substances L-carnitine and acetyl-L-carnitine: from biochemical studies to medicine

Recently reported data clarify our understanding of the molecular aspects of carnitine in medicine. Carnitine is a compound necessary for the transport of acyl-CoA across the inner mitochondrial membrane for their beta-oxidation. Only L-isomer of carnitine is biologically active. The D-isomer may actually compete with L-carnitine for absorption and transport, increasing the risk of carnitine deficiency. By interaction with CoA, carnitine is involved in the intermediary metabolism by modulating free CoA pools in the cell. Detoxification properties and anabolic, antiapoptotic and neuroprotective roles of carnitine is presented. Carnitine deficiency occurs as a primary genetic defect of carnitine transport and secondary to a variety of genetic and acquired disorders. The pathophysiological states associated with carnitine deficiency have been summarized. L-Carnitine is effective for the treatment of primary and secondary carnitine deficiencies. Acetyl-L-carnitine improves cognition in the brain, significantly reversed age-associated decline in mitochondrial membrane potential and improved ambulatory activity. The therapeutic effects of carnitine and acetylcarnitine are discussed.     

Stress protein of cyanobacteria CP36: interaction with photoactive complexes and formation of supramolecular structures

Cyanobacterium Anacystis nidulans R2, Synechocystis sp. PCC 6803 (wild-type strain and mutants Delta2 and Delta3 lacking PSII and PSI, respectively), and Synechocystis sp. BO 9201 synthesize the pigment--protein complex CP36 (CPIV-4, CP43') under iron deficiency in the medium. Accumulation of CP36 is accompanied by structural reorganizations in the photosynthetic membranes. Integrating mean times of excitation relaxation (quenching) are 2.2 nsec (CP36), 1 nsec (PSI), and 420 psec (PSII in Fm state). The energy migration between CP36 and the photosystems can be described by a model of a one-layer ring of CP36 around core-complexes. The excitation from CP36 to PSI is transferred within <10 psec. The energy transfer from CP36 to PSII occurs during 170 psec. Cells with low content of CP36 probably contain only a latent fraction of unbound to phycobilisomes PSII which is the analog of PSIIbeta of higher plants. In PSI there are four binding sites for CP36 monomers per RC. PSII can bind up to 32 molecules of CP36 per RC. Cells with a large amount of CP36 contain monomer form of PSII core-complex which can bind eight tetramers of CP36 (8 binding sites). In conditions of iron deficiency only one monomer of a dimer PSII core-complex is destroyed and released chlorophyll is accumulated in CP36. Accumulation of CP36 in A. nidulans cells can be accompanied by membrane stacking which is similar to the stacking in chlorophyll b-containing organisms. The stacking can occur in the region of localization of PSII latent fraction bound to CP36. The membrane stacking shields PSII stromal surfaces from the aqueous phase for activation of electron transfer on the acceptor side of PSII.     

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

Substrate specificity of acetyl-CoA-carboxylase from the rat liver

The interaction between acetyl-CoA fragments and rat liver acetyl-CoA carboxylase was studied. It was found that the 3'-phosphate group did not interfere with the enzyme interaction since the substrate properties of acetyl-dephospho-CoA and acetyl-CoA are nearly identical. The non-nucleotide substrate analogs S-acetyl-pantethin and its 4'-phosphate) also displayed substrate properties (V = 1.5% and 15% of the V for acetyl-CoA carboxylation respectively). The nucleotide fragment of the acetyl-CoA molecule produced an appreciable effect on the thermodynamics of this substrate interaction with the enzyme. Its physiological role consists in all probability, in the activation and propes orientation of the acetyl group in the enzyme active center. The far more pronounced substrate properties of S-acetyl pantethin 4'-phosphate and the inhibitory properties of pantethin 4'-phosphate (compared to non-phosphorylated analogs) suggest the essential role of the beta-phosphate residue of ADP in the acetyl-CoA binding to the enzyme. The data obtained suggest also that the hydrophobic region responsible for the acyl radical binding, has a site which specifically recognizes the beta-mercaptoethyl residue of the CoA pantethin fragment. The pivotal role in the acetyl-CoA carboxylase interaction with the substrate is ascribed to the productive binding of the acetyl radical; the contribution of individual fragment of the CoA molecule is variable.